Annual/Termination Reports:

[09/20/2001] [09/26/2002] [10/06/2003] [11/12/2004] [11/07/2005] [03/14/2007]

Report Information

Participants

Ames, Trevor-University of Minnesota; Baker, John-Michigan State University; Briggs, Robert-USDA, ARS, NADC; Brock, Kenny-Auburn University; Chase, Christopher-South Dakota State University; Corstvet, Richard-Louisiana State University; Czuprynski, Chuck-University of Wisconsin; Frank, Glynn-NADC; Fulton, Robert-Oklahoma State University; Loan, Raymond-Texas A&M University; Maheswaran, Sam-University of Minnesota; Minocha, Harisha-Kansas State University; Mosier, Derek-Kansas State University; Rosenbusch, Ricardo-Iowa State University; Tatum, F-NADC;

Brief Summary of Minutes

September 5, 2001, 8:30 a.m. R. Fulton called the meeting in session. Welcome comments were from R. Rosenbusch, and Don Reynolds, Associate Dean of Research, College of Veterinary Medicine, ISU. Nominations were held for 3 board members, one to be secretary for 2002. Nominees were R. Rosenbusch, A. Woolums (for secretary), and D. Grooms (A. Woolums accepted the position as secretary for 2002). Guests were introduced. Station reports were presented. Our new Administrative Advisor, Dr. E. Asem, was introduced. More station reports followed. At 11:00, our guest speaker, Dr. J. Ridpath, presented "BVDV Research." After lunch, station reports were presented until adjournment at 4:00 p.m.





September 6, 2001, 8:00 a.m. Final station report. K. Brock discussed our continuing education program with the Academy of Veterinary Consultants (bqa.org/avc/avc.htm) at their meeting in Denver, CO on Nov.30 - Dec.1, 2001. Topics for presentation were announced, along with presenters. A panel will include NC 107 members. Let K. Brock know if you plan to attend. K. Brock will send more information by e-mail to NC 107 members. Our new Advisor, E. Asem, addressed the committee. R. Fulton asked for comments on the Termination Report covering 10/1/96 - 9/30/01 to be sent to him. Meeting was adjourned 9:30 a.m.

Accomplishments

Objective 1: Define Variations in Occurrences and Enhance Methods of Surveillance and Detection of Bovine Respiratory Tract Disease (BRD) Agents:<br /> <br> A multistate project including TX, LA, OK, CA, USDA NADC, USDA/ARS Bushland, TX was involved with occurrence and etiologies of BRD. Bovine coronaviruses (BCV), bovine viral diarrhea virus (BVDV) type 1 and 2, bovine parainfluenza-3 virus (PI-3V), bovine adenoviruses, and bovine herpesvirus-1 (BHV-1) also known as IBR virus, were investigated as viral etiologies. The BCV was identified in a high percentage of cattle eventually developing BRD (TX, LA). Several methods to detect BVDV were compared by SD, AL, OK, and MI. Diagnostic laboratories in SD and WI reported on incidence of various agents of BRD. Systematic methods for strain typing of BVDV using RT-PCR along with phylogenetic analysis compared BVDV isolates. The immunoperoxidase monolayer assay for BVDV was compared to the skin biopsy technique to diagnose BVDV by MI. A molecular beacon probe system was used by SD to differentiate ruminant pestiviruses (BVDV1, BVDV2, and Border Disease virus). Improved serologic methods were used to detect infected cattle to Mycoplasma bovis by IA. PCR procedures for bovine immunodeficiency virus (BV) and BHV-5 were developed by KS.<br /> <br> Diagnostic laboratories in MN, MI, SD, NADC, and WI collected and shared data on agents isolated from BRD. In some regions there was a shift from Mannheimia haemolytica to Pasteurella multocida with low numbers of Haemophilus somnus. SD and MI collaborated with NADC and MN for serotyping of M. haemolytica. MI and WI reported on screening of dairy cattle for BVDV PI. A national survey for PI BVDV involved AL, NE, and OH. BHV-4 and BRSV were found in increased number of cases by SD and WI. <br /> <br> A survey by KS of beef stocker producers requested information on stocker demographics, calf purchasing practices, health management, disease classification, and nutrition was performed along with a survey of bovine mycoplasmosis. A serologic survey of unvaccinated calves (6-12 months old) was reported by MI to identify herds with PI animals. MS reported on BVDV in chronic BRD tract cases.<br /> <br><br /> <br><br /> <br><br /> <br>Objective 2: Define Molecular Mechanisms of Pathogenesis of Bovine Respiratory Disease:<br /> <br> Several stations investigated virulence factors of bacterial BRD including M. haemolytica (MH) leukotoxin and capsule and P. multocida, OK, KS, MS. Examples included role of Mh capsule in adherence to bovine respiratory mucosa. Also optimization of Mh leukotoxin production and LK stabilization occurred with lipopolysaccharide. The leukotoxin receptor on the CD-18 molecule was determined by NE and MN. LK in low concentrations was reported to kill bovine leukocytes by apoptosis, WI. Also leukotoxin negative Mh mutants were evaluated by OK, MN, and NADC. The SCID-Bo mouse model for Mh infection/lesions was investigated by OK and MN. MN demonstrated increases in cytokines in Mh infected lungs including TNFIL-8, and IL-1, and also the role of NF-KB activation. M. haemolytica activated a tyrosine kinase signaling cascade in bovine leukocytes and various compounds inhibited cytokine secretions in macrophages (MN). Modulation of the receptor (CD-18) by viral infection and cytokine was investigated by WI. WI investigated effects of H. somnus on bovine endothelial cells.<br /> <br> BVDV strains varied in virulence including viremia, leukopenia and platelet interactions (MI) and NE reported differences in virulence by 5&lsquo; UTR differences. NE and KS reported on differences of CP BVDV versus NCP for RNA accumulations and apoptotic activity. NE found a latency related protein for BHV-1, and BHV-1 induced down regulation of MHC. WI reported on cytotoxic T cells of cattle immunized with BHV-1. WI also reported on BHV-1 gd and gM glycoproteins. CA reported on role of BRSV for reduced tracheobronchial clearance, and developed a disease-enhancement vaccine model with BRSV. TX investigated interferon genes and resistance to BRD. KS reported on gC of BHV-5 involved with CNS disease. TX and LA were involved with genome sequencing for BCV. GA examined TNF-a expression in the lungs of BRSV infected calves and investigated bacterial pathogens and BRSV in fatal feedlot ARDS(AIP). IA utilized a mouse model for interactions of M. bovis and immune response cells.<br /> <br><br /> <br><br /> <br><br /> <br>Objective 3: Improve Strategies for the Prevention and Control of Respiratory Disease:<br /> <br> New immunogen for BHV-1 and P. multocida were studied by NE and OK. Mucosal defense mechanisms were investigated by MO and LA. TX and NADC continued studies on antibiotic metaphylaxis and vaccination combination in stressed calves. MLV and killed viral vaccines were studied by MI and OK. OK reported on onset and duration of serum antibodies in calves receiving viral and ML vaccines. NE studied CMI responses in epitope based vaccines using responses to epitope based vaccines using cytotoxic T-lymphocyte peptides of BHV-1 complexed with heat shock protein. Intranasal vaccination in rabbits with iron regulated OMP from P. multocida induced protective immune response (OK). OK also characterized a filamentous hemagglutinin protein from P. multocida. GA evaluated intranasal BRSV vaccination by measuring CMI response in calves. Several stations reported on gene based vaccines. MI reported use of adenovirus vector vaccine for BVDV. WI used a biolistic (gene gun) vaccine for BHV-1, and CA used constructed plasmid vectors for cDNA BRSV vaccine. LA reported benefits of intransal MH vaccines by preventing lung infections.<br /> <br> The economic impact of PI BVDV exposure to calves is subject of AL and MI study. The transmission of M. bovis in calves was compared to other bacterial pathogens (IA). An Mh leukotoxin deficient live vaccine was evaluated in sale barn calves and fresh ranch calves with resultant increased serum antibodies and reduced Mh colonization by wild-type Mh.<br /> <br>

Publications

Brogden, K.A., Kalfa, V.C., Ackermann, M.R., Palmquist, D.E., McCray, P.B., Jr., and Tack, B.F. The ovine cathelicidin SMAP29 kills ovine respiratory pathogens in vitro and in an ovine model of pulmonary infection. Antimicrob. Agents Chemother 45:331-334, 2001.<br /> <br><br /> <br>Butler, J.A., C.C. Pinnow, J.U. Thomson, S. Levisohn, and R.F. Rosenbusch. 2001. Use of arbitrarily primed polymerase chain reaction to investigate Mycoplasma bovis outbreaks. Vet Microbiol. 78: 175-181.<br /> <br><br /> <br><br /> <br>Caverly, J.M., Radi, Z.A., Andreasen, C.B., Doxon, R.A., Brogden, K.A., and Ackermann, M.R. Comparison of bronchoalveolar lavage fluid obtained from Mannheimia haemolytica-inoculated calves with and without prior treatment with the selection inhibitor TBC1269. Am. J. vet. Res. 62:665-672, 2001.<br /> <br><br /> <br><br /> <br>Chapes S.K., Mosier D.A., Wright A.D., Hart M.L.: MHCII, T1r4, Nramp1 genes control host pulmonary resistance against the opportunistic bacterium Pasteurella pneumotropica. J. Leukocytes Biol., 69:381-386, 2001.<br /> <br><br /> <br><br /> <br>Clarke, J.M., Morton, R.J., Clarke, C.R., Fulton, R.W., Saliki, J.T., and Malayer, J.: Development of an ex vivo Model to study Adherence of Mannheimia haemolytica serovar A1 to Mucosal Tissues of the Upper Respiratory Tract of Cattle. Am. J. Vet. Res., 62:805-811, 2001.<br /> <br><br /> <br><br /> <br>Confer AW, Suckow MA, Montelongo M, Dabo SM, Miloscio LJ, Gillespie AJ, and GL Meredith. Intranasal vaccination of rabbits with Pasteurella multocida A:3 outer membranes expressing iron-regulated proteins. Am J Vet Res 62:697-703, 2001..<br /> <br><br /> <br><br /> <br><br /> <br>Hegde, N.R., Godson, D.L., Babiuk, L.A. and Srikumaran, S. 2001. Bovine lymphocyte antigen-A11-specific peptide motif as a means to identify cytotoxic T lymphocyte epitopes of bovine herpesvirus 1. Cellular Immunology, Submitted.<br /> <br><br /> <br><br /> <br><br /> <br>Hinkley S, AB Hill, and S Srikumaran. 2001. Bovine herpesvirus 1 infection affects the peptide transport activity of TAP in bovine cells. Virus Res. Submitted.<br /> <br><br /> <br>Hossain A, T Holt, and C Jones. 2001. Analysis of cyclins and cyclin dependent kinases after an infection with herpes simplex virus type 2. J Gen Virol. In press.<br /> <br><br /> <br><br /> <br>Inman, M., Y. Zhange, V. Geiser, and C. Jones. 2001. The zinc ring finger of bovne herpes virus 1 encoded biCPO is necessary for transcriptional regulation and infection. J. Gen. Virology 82:483-492.<br /> <br><br /> <br><br /> <br><br /> <br>Jeyaseelan, S., M.S. Kannan, S.L. Hsuan, A.K. Singh, T.F. Walseth, and S.K. Maheswaran. 2001. Pasteurella haemolytica leukotoxin-induced cytolysis of bovine leukocytes: Role of arachidonic acid and its regulation. Microb. Pathog. 30:59-69.<br /> <br><br /> <br><br /> <br><br /> <br>Kalfa V.C. Palmquist, D., Ackermann, M.R., and Brogden, K.A. (2001). Suppression of Mannheimia (Pasteurella) haemolytica serovar 1 infection in lambs by intrapulmonary administration of ovine antimicrobial anionic peptide. Int J Antimicrob Agents. 17:505-10.<br /> <br><br /> <br><br /> <br><br /> <br>Kirkpatrick, J., Fulton, R.W., Burge, L.J., Dubois, W.R., and Payton, M. 2001): Passively Transferred Immunity in Newborn Calves, Antibody Decay, and Effect on Subsequent Vaccination with Modified Live Virus Vaccine. Bovine Practitioner, 35:47-55.<br /> <br><br /> <br><br /> <br><br /> <br>Loan RW, Purdy CW, Briggs RE: Additive effect of antibiotic metaphylaxis and Pasteurella haemolytica bacterin vaccination. In revision for the Bovine Practitioner, June, 2001.<br /> <br><br /> <br><br /> <br>Loughmiller J.A., spire M.F., Dritz S.S., Fenwick B.W., Hosni M.H., Hogge S.B.: Relationship between mean body surface temperature measured by use of infrared thermography and ambient temperature in clinically normal pigs and pigs inoculated with Actinobacillus pleuropneumoniae. Am. J. Vet. Res., 62:676-681, 2001.<br /> <br><br /> <br><br /> <br>Malazdrewich, C., T.R. Ames, M.S. Abrahamsen, and S.K. Maheswaran. 2001. Pulmonary expression of tumor necrosis factor-alpha, interleukin-beta, and interleukin-8 in the acute phase of bovine pneumonic pasteurellosis. Vet. Pathol. 38:297-310.<br /> <br><br /> <br><br /> <br><br /> <br>Navaratnam, M., M. Desphande, M.J. Hariharan, D.S. Zatechka Jr. and S. Srikumaran. 2001. Heat shock protein-peptide complexes elicit cytotoxic T-lymphocyte and antibody responses specific for bovine herpesvirus 1. Vaccine. 19:1425-1434.<br /> <br><br /> <br><br /> <br>Radi, Z.A., Caverly, J.M., Dixon, R.A., Brogden, K.A., and Ackermann, M.R. (2001) Effects of the synthetic selectin inhibitor TBC1269 on tissue damage during acute Mannheimia haemolytica-induced pneumonia in neonatal calves. Am. J. Vet. Res. 62:2684-2691.<br /> <br><br /> <br><br /> <br><br /> <br>Salih, B.A., and R.F. Rosenbusch. 2001. Cross-reactive proteins among eight bovine mycoplasmas detected by monoclonal antibodies. Comp. Immunol. Microbiol. Infect. Dis. 24:103-111.<br /> <br><br /> <br><br /> <br><br /> <br>Sylte, M.J., L. B. Corbeill, and C.J. Czuprynski. 2001. Haemophilus somnus causes apoptosis in bovine endothelial cells in vitro. Infect. Immun. 69:1650-1660.<br /> <br><br /> <br><br /> <br><br /> <br>Wittum, T.E., D. M. Grotelueschen, K.V. Brock, W. Kvasnicka, J. Floyd, C.L. Kelling and K.G. Odde. 2001. Persistent bovine viral diarrhea virus infection in beef herds. Veterinary Preventive Medicine 49:83-84.<br /> <br><br /> <br><br /> <br>Zhao, C., Nguyen, T., Lui, L., Sacco, R.E., Brogden, K.A., and Lehrer, R.I. Gallinacin-3, an inducible epithelial beta-defensin in the chicken. Infect. Immun. 69:2684-2691, 2001.<br /> <br><br /> <br><br /> <br>Zheng L, Swanson M, Liao J, Wood C, Kapil S, Snider R, Loughin T, and H Minocha. 2001. Cloning of the Bovine Immunodeficiency Virus Gag Gene and Development of a Recombinant-Protein Based Enzyme-Linked Immunosorbent Assay. Clin Diag Lab Immunol 7:557-562.<br /> <br><br /> <br><br /> <br>Zheng, L., Zhang S., Wood C., Kapil S., Wilcox G., Loughin T., Minocha H.: Differentiation of two bovine Lentiviruses by a monoclonal antibody on the basis of epitope specificity. Clin. Diagn. Lab. Immunol. 3:283-287, 2001.<br /> <br><br /> <br>

Impact Statements

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Report Information

Participants

Baker, John (baker@cvm.msu.edu) - Michigan State U;
Briggs, Robert (bbriggs@nadc.ars.usda.gov) - USDA, ARS, National Animal Disease Center;
Brock, Kenny (brockkv@vetmed.auburn.edu) - Auburn U;

Chase, Chris (christopher_chase@sdstate.edu) - South Dakota State U;
Corstvet, Richard (rcorst1@lsu.edu) Louisiana State U.

Czuprynski, Chuck (czuprync@svm.vetmed.wisc.edu) - U of Wisconsin;
Fulton, Robert (rfulton@okstate.edu) - Oklahoma State U;
Frank. Glynn (gfrank@nadc.ars.usda.gov) - USDA, ARS, National Animal Disease Center;
Grooms, Dan (groomsd@cvm.msu.edu) - Michigan State U;
Hurley, David (dhurley@vet.uga.edu) - U of Georgia;
Loan, Raymond (rloan@cvm.tamu.edu) - Texas A&M U;
Maheswaran, Sam (mahes001@tc.umn.edu) - U of Minnesota;
Rosenbusch, Ricardo (rfrosenb@iastate.edu) - Iowa State U;
Walz, Paul (pwalz@vet.ksu.edu) - Kansas State U;
Woolums, Amelia (awoolums@vet.uga.edu) - U of Georgia;
Eli Asem (asem@purdue.edu). Purdue University, Administrative Advisor

Brief Summary of Minutes

ADOPTED AGENDA: September 10: 7:30, registration; 8:15, welcome (Dr. Grooms) and introduction to Michigan State University (Dr. Baker) and Michigan Agricultural Experiment Station (Dr. Gray). 8:30-9:00, station reports. 9:00, presentation of plans for new diagnostic laboratory by Dr. Reed, Director of Michigan State Veterinary Diagnostic Laboratory. 9:30-12:00, station reports. 12:00-1:00, Lunch. 1:00-2:00, business meeting. 2:00-4:45, station reports. 4:45, adjourn. September 11: 8:15, resume station reports. Adjourn 9:30.





KEY DISCUSSIONS: During his welcome to Michigan State University, Dr. Baker described new developments at Michigan State of interest to the group, including the new center for Emerging Animal Diseases. Dr. Ian Gray, Director of the Michigan Agricultural Experiment station, further detailed new developments of interest, particularly the Animal Industrial Initiative which has significantly expanded animal disease research efforts at Michigan State University. As chair of the NC administrative advisors, Dr. Gray also advised the group to recount their activities and efforts in written reports in clear detail. Dr. Willie Reed, Director of the Michigan State Veterinary Diagnostic Laboratory, described plans for the new Diagnostic Laboratory which is currently under construction. The laboratory will have BL3 areas for necropsy and microbiology work and will also have facilities to house over 300 cattle, which will be valuable when herd depopulations are required. These facilities will improve the ability of Michigan to control tuberculosis, currently a serious problem for Michigan cattle and wildlife. Station reports continued for the rest of the morning of September 10. The business meeting, chaired by Dr. Glynn Frank, began at 1 PM. First order of business: election of a new secretary. It was moved and seconded that Dr. Dan Grooms be nominated; the group unanimously elected Dr. Grooms as the next secretary. Minutes from previous meeting approved as written.





The site for 2003 technical committee meeting was then discussed. Dr. Maheswaran suggested Minnesota. Dr. Corstvet also invited the group to Louisiana State University (LSU). Many new faculty members and new developments at LSU will increase activities of interest to NC-107. Change of date of meeting was discussed. It was proposed that small number in attendance may have been due to time of year. Others suggested that fall is best time and that small numbers in attendance were not concerning, as the meeting is not a scientific meeting but rather a technical committee meeting; purpose is for voting member to attend and give report. Lack of participation by some stations was discussed. It was suggested that Dr. Asem could talk to directors at nonparticipating states about whether they are going to become active. It was noted that some stations intended to have reps here this year but unexpected developments prevented them from attending; at other stations (e.g. Tennessee) most involved people have left. The question was raised as to whether states are required to participate if they are in the North Central region; the consensus was that they are not. Dr. Asem read the states that agreed to participate in new project: AL, CA, GA, IA, KS, LA, MI, MN, MS, MO, NE, OH, OK, SD, TX, WI, NADC. Stations on this list who have not presented report can be asked why they have not sent their reports. It was agreed that states not on this list would no longer be considered participating (e.g., reports would no longer be expected from states not on this list in spite of past participation). It was noted that the voting members from MO (Dr. Estes) and MS (Dr. Paulsen) had recently moved; it was not clear who would replace them although Dr. J. Lakritz had been registered to attend from MO and Dr. Dan Scruggs was mentioned as a possible participant from MS. It was agreed that Dr. Asem would contact station directors of states with spotty or no participation to determine whether they should be removed from the project.





Was moved and seconded that technical committee would meet at LSU next year; the vote was unanimous in favor of this. The date of future meetings was discussed; consensus was that early September was still best, although possible impact of historical events on September 11 were recognized. It was agreed that the host would need some latitude in scheduling. Current plan is for next year‘s meeting to occur on September 9 and 10; Dr. Corstvet, who will make local arrangements, will confirm date later in year.





Question was raised as to why no one from USDA or NVSL was in attendance. Dr. Frank has spoke with Dr. Ruby at NVSL; they are very busy with West Nile Virus and other problems. It was noted that USDA representatives from Washington are not routinely expected to attend; the administrative advisor keeps them informed. The consensus of the group was that this was an appropriate strategy.





Dr. Asem distributed notes from NCRA guidelines, which suggest that Chair, Chair-Elect, and secretary be elected for 2-year term. This committee has traditionally had officers for one-year term. Committee discussed this and agreed they would like to continue with no chair-elect and with single year terms for Chair and Secretary. A motion was made and seconded that election of officers would continue as in the past; the vote in favor was unanimous.





Dr. Asem noted that the Proceedings of Academy of Consultants 2001 Winter Meeting, where NC-107 members made up the majority of the program, were an excellent example of the types of outreach expected by regional research projects. He will send a copy to USDA administrators in Washington. Copies of the Proceedings were distributed to those in attendance. Dr. Asem commended group for activity and strong leadership.





Preparation of interim report and annual reports was discussed at length. It was clarified that the interim report would be written at end of year 3; this is currently end of first year. Dr. Asem distributed a copy of SAES-422, which details the format for annual reports as they are to be entered on the world wide web. Dr. Frank will complete the annual report this year and Dr. Asem will enter the report onto the website. Noted that accomplishments and impact need to be clearly and separately identified in individual station annual reports, which will simplify generation of annual report for Chair (who traditionally generates the annual report for this group, rather than the Secretary). Question was raised whether cooperative research between stations is still important; importance of such efforts were emphasized very much in the past. Dr. Asem concurred that it is still very important and will need to be clearly outlined in 5-year report. There was concern that latest version of format for project annual report does not specifically have a section for listing inter-station collaboration. It was agreed that stations should continue to list inter-station collaboration in their individual reports and that a summary of such collaboration should be included, possibly in the Accomplishments section, of the annual report. It was agreed that is was important to keep a record in each year‘s annual report of inter-station collaborations so the information would not be lost when it is time to compile the 5-year report.





Dr. Asem distributed Appendix L, guidelines re development of website for technical committee, which is recommended by NCRA. Also NCRA suggests that a listserve be developed to facilitate communication within regional projects. The group discussed this issue and agreed that a dedicated webmaster would be necessary to ensure success of a webpage, but that no one in the group was likely to have the time, expertise, or funding to support or act as a dedicated webmaster. The consensus was that the group is small enough and communicates well enough that a listserve or website would not be worth the time and effort they would require to maintain.





Dr. Asem then briefly reviewed the approach used by the NCA-2 committee in review of annual reports from regional projects. As the administrative advisor for another regional research project, Dr. Baker is also on this committee with Dr. Asem. Annual reports are reviewed and summarized by 2-3 people on the NCA-2 committee. Many reports lack clarity and it is hard to find information easily. Specifically, reports are expected to show evidence of use of strengths of individual stations combined with evidence of cooperation between stations. Dr. Asem indicated that there have been no problems with annual reports from NC-107, he presented the information just to give the group insight on the procedure used in evaluation of annual reports.





The issue of accountability for objectives set out for individual stations in the new project description was discussed. The question was raised whether administrators evaluating annual or interim reports would evaluate whether stations really accomplished what they said they would accomplish when the project was renewed. Several members felt that it was not necessary to specifically detail whether or not each objective was actually accomplished by each station. However, the consensus was that it was beneficial to periodically refer to the list of objectives set out when the project was renewed to try to keep on track with milestones established at the beginning of the project. Dr. Asem‘s role in part is to assure the group‘s accountability.





The business meeting was concluded at 2:10; station reports resumed at 2:30 after a short break. The meeting was adjourned at 4:45 with 3 station reports left for September 11. The group reconvened at 8:10 AM on September 11 with continuation of station reports. The meeting was adjourned at 9:35 AM.





Assigned responsibilities/deadlines/target dates: Dr. Frank will prepare this year‘s annual report and forward to Dr. Asem for submission. Dr. Woolums (Chair for 2002-2003) will communicate with Dr. Corstvet (in charge of local arrangements for the 2003 meeting) and Dr. Asem in coming months to distribute information regarding the next meeting. Dr. Woolums will distribute updated address list for group.





Next meeting information: September 9 and 10, 2003, at Louisiana State University, Baton Rouge, LA.

Accomplishments

OBJECTIVE 1: Identify emerging and re-emerging agents and develop diagnostic methods for bovine respiratory disease (BRD).<br /> <br><br /> <br>California: Infection with Hemophilus. somnus on day 6 of BRSV infection leads to a longer febrile period, persistent cough, and a more severe lesion at necropsy.<br /> <br><br /> <br>Kansas State: Virus isolation and three different regions of the bovine virus diarrhea virus (BVDV) genome probed by RT-PCR, were compared for their variation in detection of 40 BVDV field isolates. There was variability in virus detection between the detection methods. The relationship between BVDV biotype and genotype and characteristics of the resulting disease were examined for 117 isolates. Specific disease syndromes were not confined to specific virus biotypes or genotypes.<br /> <br><br /> <br>Michigan: The usefulness if IHC for identifying neonatal calves persistently infected with BVDV was evaluated and determined to be very accurate.<br /> <br><br /> <br>Minnessota: The infectious agents associated with BRD were monitored by bacterial culture, virus isolation, viral serum neutralization tests, direct fluorescent antibody techniques (DFA), immunohistochemistry (IH), and PCR tests.<br /> <br><br /> <br>Mississippi: Persistent BVD virus infection was more prevalent in light weight placement cattle than in heavier weight placement cattle. Most positive cattle were identified as sick and pulled within the first 10 days on feed. <br /> <br><br /> <br>Oklahoma: Serum concentrations of four acute phase proteins (fibrinogen [Fb], haptoglobin [Hp], serum amyloid-A [SAA], and a-1 acid glycoprotein [AGP]) were evaluated as either prognostic or diagnostic tools regarding the occurrence of bovine respiratory disease in marketing and shipping stressed feedlot cattle. <br /> <br><br /> <br>Wisconsin: Of bovine viral pathogens tested for during the year 2001, the highest percentage of positive tests was for BRSV.<br /> <br><br /> <br>Iowa: Nasal sampling for Mycoplasma.bovis was found to be predictive of the biotypes of the mycoplasma found in tracheal wash samplings from the same calf. Phenotyping of strains by antibiotic sensitivity was found to be more discriminating than genomic fingerprinting. <br /> <br><br /> <br>South Dakota: Principal respiratory pathogens were similar to preceding years with Pasteurella multicida, Mannheimia haemolytica, and noncytopathic BVDV most frequently isolated.<br /> <br><br /> <br>OBJECTIVE 2: Characterize mechanisms and intervention targets in pathogenesis of BRD at the molecular, cellular, and host level.<br /> <br><br /> <br>Kansas State: A Bovine Herpes Virus-5 (BHV-5) Us9-deleted recombinant was generated and its neurovirulence and neuroinvasive properties were compared with a Us9-rescued BHV-5 in a rabbit model. Experimental infections indicated that Us9 is essential for the anterograde spread of the virus from the olfactory mucosa to the bulb. <br /> <br><br /> <br>Kansas State: Using PCR amplification and southern blot hybridizations, portions of the ToxA gene of Pasteurella multocida are conserved in Mannheimia haemolytica isolates. Leukotoxin production by M. haemolytica is significantly greater when the organism is cultured in reduced oxygen conditions.<br /> <br><br /> <br>Minnessota: Dexamethazone pretreatment reduced symptoms of clinical disease and gross lung pathology in calves experimentally infected with M. haemolytica. <br /> <br><br /> <br>Mississippi: DNA adenine methylation in P. multocida and M. haemolytica have been demonstrated. The P. multocida dam gene was cloned and over-expression mutants of P. multocida have been constructed.<br /> <br><br /> <br>National Animal Disease Center: An immunoglobulin-binding protein was demonstrated in whole cell sonicate and culture supernatant preparations from an M. haemolytica serotype 1.<br /> <br><br /> <br>Nebraska: Down-regulation of class I molecules by BHV-1 is mediated by vhs activity of the virus, as well as mechanism(s) specifically directed at the class I pathway. <br /> <br><br /> <br>Nebraska: Mechanisms of BHV-1 latency in relation to latency related genes were studied. <br /> <br><br /> <br>Nebraska: Subpopulations of lymphocytes were more markedly altered in peripheral blood (PBL) and lymphoid tissues from co?infected calves compared to calves infected with either BRSV or BVDV alone.<br /> <br><br /> <br>Nebraska: Extensive apoptosis of dendritic cells and lymphocytes occurred in the cortex of mesenteric lymph nodes of calves infected with BVDV.<br /> <br><br /> <br>Nebraska: Expression of the mouse Fc@ receptor B2 in bovine cells rescues the infectivity of conditionally neutralized BVDV.<br /> <br><br /> <br>Nebraska: The envelope glycoprotein E2 is a determinant of host range in ruminant pestiviruses.<br /> <br><br /> <br>Nebraska: Bovine CD18 is necessary and sufficient to mediate Mannheimia (Pasteurella) haemolytica leukotoxin-induced cytolysis. <br /> <br><br /> <br>Oklahoma: Three outer membrane proteins (OMPs) including a 95 kDa OMP from a bovine P. multocida grown in iron-depleted conditions were described.<br /> <br><br /> <br>Texas: Accomp: There was no association of the specific polymorphisms in the AMPK gene family of the bovine and the incidence of BRD.<br /> <br><br /> <br>Wisconsin: Continued their investigations of the effects of M. haemolytica leukotoxin, cytokines, and BHV-1 on bovine leukocytes.<br /> <br> <br /> <br>Wisconsin: We have obtained histochemical evidence of vasculitis in tissues from calves with spontaneous H. somnus infection, and find immunohistochemical evidence of apoptotic endothelial cells.<br /> <br><br /> <br>Georgia: Cytokine expression following virulent BRSV challenge was studied.<br /> <br><br /> <br>Georgia: Bacterial respiratory pathogens are associated with some cases of feedlot AIP, but in many cases bacterial respiratory pathogens are not isolated, even when animals have no history of antimicrobial therapy. Lesions indicate that some previous airway insult has occurred in animals with AIP. <br /> <br> <br /> <br>Iowa: A lymphotoxic activity is described for Mycoplasma bovis, and this virulence factor was not observed in other species of bovine mycoplasmas. <br /> <br><br /> <br>South Dakota: Molecular pathogenesis studies with BVDV were conducted. BVDV infected macrophages down regulated MHC Class I and II and CD 14 surface markers. This down regulation correlated with the in vivo pathogenicity of the isolates with persistent infection strains down regulating MHC Class I and the acute disease strains down regulating MHC Class II and CD 14. IFN-alpha inhibited BVDV replication and RNA synthesis and its effect was dose, time and biotype dependent. It also indicated that IFN inhibition of virus replication was carried out through inhibition of viral RNA production and independent of the PKR pathway. CP/BVDV induced apoptosis as early as 24 hours post infection; p53 and caspase pathways were involved in the BVDV apoptosis.<br /> <br><br /> <br><br /> <br>OBJECTIVE 3: Develop intervention strategies for critical control points to reduce the impact of BRD.<br /> <br><br /> <br>Alabama: Evaluated bo-SKID mice as an alternate model for evaluation of antiviral compounds against BVDV. Identified 6 potential antiviral compounds. Demonstrated that cattle persistently infected with BVDV negatively impact feedlot cattle.<br /> <br><br /> <br>Louisiana: BHI cell free supernatant of M. haemolytica contained 28-kD, 45-kD, 63-kD and 130-kD bands. Antibody to the 28kD and 30-kD bands apparently are important in determination of recent exposure to the bacterium.<br /> <br><br /> <br>Michigan: Calves persistently infected with BVDV impact the performance of cohort feedlot cattle by increasing morbidity and decreasing average daily gain.<br /> <br><br /> <br>National Animal Disease Center: Vaccination of calves with live lktA- MH/acapsular PM before transport had little measurable effect on RTD and colonization. <br /> <br><br /> <br>National Animal Disease Center: Defensin induced adaptive immunity in mice. Congeners of SMAP29 kill ovine pathogens and induce ultrastructural damage in bacterial cells.<br /> <br><br /> <br>Oklahoma: Herds with a low morbidity rate had higher levels of BVDV1a antibodies than herds with a high morbidity rate. On both an individual-animal and a herd-average basis, calves with low levels of antibody to BVDV1a and BVDV2 had increased total treatment costs. Also, for individual animals and the herd as a whole, low levels of antibody to P. multocida, BVDV1a, and BVDV2 were related to decreased net value to owner (carcass value minus total feedlot cost). <br /> <br><br /> <br>Wisconsin: There was no difference in serum antibody titers when modified live BRSV vaccine was given IN and SC, as compared to SC alone.<br /> <br><br /> <br>Georgia: Cytokine expression following virulent BRSV challenge in vaccinated calves was studied. <br /> <br><br /> <br>Iowa: Calves infected intratracheally with Mycoplasma bovis responded with a Th2-like response characterized by IL-4 production by PBMCs subjected to in-vitro recall response, and antigen-specific IgG1 serum antibody response. The response may enhance lung lesion development and result in slow clearance of the organism from lung.<br /> <br><br /> <br>South Dakota: Isoflavones fed to cattle had a small effect on bovine herpesvirus 1 and no effect on NCP-BVDV type 1.<br /> <br><br /> <br>Texas: Dual prophylaxis reduces the incidence and severity of BRD as compared to metaphylaxis alone.<br /> <br>

Publications

Akula S, DJ Hurley, RL Wixon, C Wang and CCL Chase. 2002. Effect of genistein on replication of bovine herpesvirus type 1. Am. J. Vet. Res.63:1124-1128.<br /> <br><br /> <br><br /> <br>Ambagala AP, Z. Feng, RG, Barletta, S. Srikumaran. 2002. Molecular cloning, sequencing, and characterization of bovine transporter associated with antigen processing 2 (BoTAP2). Immunogenetics 54:30-38.<br /> <br><br /> <br><br /> <br>Brock KV, Cortese VS. Experimental fetal challenge using type II bovine diarrhea virus in cattle vaccinated with a modified-live virus vaccine. Vet therapeutics 2001;2:354-360.<br /> <br><br /> <br><br /> <br>Butler JA, CC Pinnow, JU Thomson, S. Levisohn, RF Rosenbusch. <br /> <br>2001. Use of arbitrarily primed polymerase chain reaction to investigate <br /> <br>Mycoplasma bovis outbreaks. Vet. Microbiol. 78: 175-181.<br /> <br><br /> <br><br /> <br>Champlin FR, TR Shryock, CE Patterson, FW Austin, PE Ryals. 2002. Prevalence of a novel capsule-associated lipoprotein among Pasteurellaceae pathogenic in animals. Curr. Microbiol. 44:297-301.<br /> <br><br /> <br><br /> <br>Chouljenko VN, XQ Lin, J Storz, KG Kousoulas, 2001. Elucidation of the genomic nucleotide sequence of bovine coronavirus and analysis of cryptic leader mRNA fusion sites. Adv. Exp. Med. Biol. 2002. 494:49-55.<br /> <br><br /> <br><br /> <br>Chouljenko VN, Lin XQ, Storz J, Kousoulas KG, Gorbalenya AE. 2001. Comparsion of genomic and predicted amino acid sequences of respiratory and enteric bovine coronaviruses isolated from the same animal with fatal shipping pneumonia. J Gen Virol 82:2927-2933.<br /> <br><br /> <br><br /> <br>Chowdhury SI, Onderci M, Bhattacharjee PS, Al-Mubarak A, Weiss ML, Zhou Y. (2002). Bovine herpesvirus 5 (BHV-5) Us9 is essential for BHV-5 neuropathogenesis. J. Virol. 76: 3839- 3851.<br /> <br><br /> <br><br /> <br>Confer AW, Suckow MA, Montelongo M, Dabo SM, Miloscio LJ, Gillespie AJ, Meredith GL. Intranasal vaccination of rabbits with Pasteurella multocida A:3 outer membranes expressing iron-regulated proteins. Amer J Vet Res 62:697-703, 2001.<br /> <br><br /> <br><br /> <br>Confer AW, Montelongo M, Brown MJ, Fergen BJ, Clement JC. Onset of Serum Antibodies to Pasteurella (Mannheimia) haemolytica following vaccination with five commercial vaccines. Bov Practitioner 35: 141-148, 2001.<br /> <br><br /> <br><br /> <br>DeBey BM, Lehmkuhl HD, Chard?Bergstrom C, Hobbs LA. Ovine adenovirus serotype 7?associated mortality in lambs in the US. Vet. Pathol. 2001:38 644?648.<br /> <br><br /> <br><br /> <br>Fales-Williams AJ, Gallup JM, Ramirez-Romero R, Brogden K., Ackermann MR. Increased anionic peptide distribution and intensity during progression and resolution of bacterial pneumonia. Clin. Diagn. Lab. Immunol. 2002:1, 28-32.<br /> <br><br /> <br><br /> <br>Fent GM, Fulton RW, Saliki JT, Caseltine SL, Lehmkuhl HD, Confer AW, Purdy CW, Briggs RE, Loan RW, Duff GC. Bovine adenovirus-7 infections in postweaning calves. Am. J. Vet. Res. 63:976-978, 2002.<br /> <br><br /> <br><br /> <br>Flores EF, GR Risatti, et al. (2002). Expression of the mouse Fc receptor B2 in bovine cells rescues the infectivity of conditionally neutralized bovine viral diarrhea virus. Vet. Microbiol. 85: 99-109.<br /> <br><br /> <br><br /> <br>Frank GH, Briggs RE, Duff GC, Loan RW, Purdy CW. Effects of pretransit vaccination and arrival medication with florfenicol on the health of transported calves and the presence of Mannheimia haemolytica organisms in nasal secretions. Am. J. Vet. Res. 2002: 63, 251?256.<br /> <br><br /> <br><br /> <br>Frazier M, Pence M, Mauel MJ, Ligget A, Hines ME, Sangster L, Lehmkuhl HD, Miller D, Styer E, West J, Baldwin CA. Endometritis in postparturient cattle associated with bovine herpesvirus?4 infection: 15 cases. J. Diagnos. Invest. 2001: 13, 502?508.<br /> <br><br /> <br><br /> <br>Fulton RW, Cook BJ, Step DL, Confer AW, Saliki JT, Burge LJ, Welsh RD, Blood KS, Payton MD. Evaluation of animal health status of calves and their impact on feedot performance: Assessment of a retained ownership program of postweaning calves. Can. J. Vet. Res. 66:173-180, 2002.<br /> <br><br /> <br><br /> <br>Fulton RW, Ridpath JF, Saliki JT, Briggs RE, Confer AW, Burge LT, Purdy CW, Loan RW, Duff GC, Payton ME. Bovine viral diarrhea virus (BVDV)1b: Predominant subtype in calves with respiratory disease. Can. J. Vet. Res. 66:181-190, 2002.<br /> <br><br /> <br><br /> <br>Gatto NT, Dabo SM, Hancock RE, Confer AW. Characterization of, and immune responses of mice to, the purified OmpA-equivalent outer membrane protein of Pasteurella multocida serotype A:3 (Omp28),. Vet Microbiol 87:221-235, 2002.<br /> <br><br /> <br><br /> <br>Givens MD, Galik PK, Riddell KP, Stringfellow DA, Brock KV, Bishop MD, Eilertsen KJ, Loskutoff NM. Validation of a reverse transcription nested polymerase chain reaction (RTnPCR) to detect bovine virus diarrhea virus (BVDV) associated with in vitro-derived bovine embryos and co-cultured cells. Theriogenology 2001;56:787-799.<br /> <br><br /> <br><br /> <br>Grooms DL, Kaiser L, Walz PH, Baker JC. Study of cattle persistently infected with bovine viral diarrhea virus that lack detectable virus in their serum. J Am Vet Med Assoc, 2001;219:629-631.<br /> <br><br /> <br><br /> <br>Grooms DL, Coe PH. Antibody response following vaccination for respiratory viruses in preconditioned calves. Vet. Therap. 3;119-127<br /> <br><br /> <br><br /> <br>Grooms DL, Keilan E. Screening of neonatal calves for bovine viral diarrhea virus by immunohistochemistry on skin samples. Clin Diagn Lab Immun, 9:898-900. 2002<br /> <br><br /> <br><br /> <br>Guey-Chuen P, B. Maguen, L. Jing, K.R. Mott, N. Osorio, S.M. Slanina, A. Yukht, H. Ghiasi, A.B. Nesburn, M. Inman, G. Henderson, C. Jones, and S.L. Wechsler. 2002. A gene capable of blocking apoptosis can substitute for the herpes simplex virus type 1 LAT gene and restore wild type reactivation levels. J. Virol. 76:1224-1235.<br /> <br><br /> <br><br /> <br>Hart ML, Mosier DA, Chapes SK.: The response of Tlr-4-receptor positive cells to infection. 35th Annu. Soc. for Leuk. Biol., Honolulu, HI, 2001. J. Leukocyte Biol. supp., 67, 2001.<br /> <br><br /> <br><br /> <br>Inman M, Y. Zhange, V. Geiser, and C. Jones. 2001. The zinc ring finger of bovine herpes virus 1 encoded bICP0 is necessary for transcriptional regulation and infection. J. Gen. Virol. 82:483-492. <br /> <br><br /> <br><br /> <br>Inman M, L Lovato, A. Doster, and C. Jones. 2001. A mutation in the latency related gene of bovine herpesvirus 1 leads to impaired ocular shedding in acutely infected calves. J. Virol. 75:8507-8515.<br /> <br><br /> <br><br /> <br>Jeyaseelan,S., M.S. Kannan, R. E. Briggs, P. Thumbikat, and S. K. Maheswaran. 2001. Mannheimia haemolytica leukotoxin activates a non-receptor tyrosine kinase-signaling cascade in bovine leukocytes which induces biological activity. Infect. Immun. 69: 6131-6139.<br /> <br><br /> <br><br /> <br>Jeyaseelan S, MS Kannan, SL Hsuan, AK Singh, TF Walseth, S.K.Maheswaran. 2001. Pasterella haemolytica leukotoxin - induced cytolysis of bovine leukocytes: Role of arachidonic acid and its regulation. Microb. Pathog. 30: 59-69. <br /> <br><br /> <br><br /> <br>Kalfa VC, Jia HP, Kunkle RA, McCray Jr. PB, Tack BF, Brogden KA. Congeners of SMAP29 kill ovine pathogens and induce ultrastructural damage in bacterial cells. Antimicrob. Agents Chemother. 45:3256-3261, 2001.<br /> <br><br /> <br><br /> <br>Lafleur RL,C. Malazdrewich, S Jeyaseelan, E Bleifield, MS Abrahamsen, SK Maheswaran. 2001. Lipopolysaccharide enhances cytotolysis and inflammatory cytokine induction in bovine alveolar macrophages exposed to Pasteurella (Mannheimia) haemolytica leukotoxin. Microb. Pathog. 30: 347-357.<br /> <br><br /> <br><br /> <br>Leite F, M. Sylte, S O&lsquo;Brien, R Schultz, S Peek, K. Van Reeth and C. Czuprynski 2001. Effect of experimental infection of cattle with bovine herpesvirus-1 on the ex vivo interaction of bovine leukocytes with Mannheimia haemolytica leukotoxin. Vet. Immunol. Immunopathol. 84: 97-110.<br /> <br><br /> <br><br /> <br>Leite F, S O&lsquo;Brien, MJ Sylte, T Page, D Atapattu, and CJ Czuprynski. 2002. Inflammatory cytokines enhance the interaction of Mannheimia haemolytica leukotoxin with bovine peripheral blood neutrophils in vitro. Infect. Immun. 70:4336-4343.<br /> <br><br /> <br><br /> <br>Malazdrewich C, TR Ames, MS Abrahamsen, SK Maheswaran. 2001. Pulmonary expression of tumor necrosis factor - alpha, interleukin - beta, and interleukin - 8 in the acute phase of bovine pneumonic pasteurellosis. Vet. Pathol.38: 297-310.<br /> <br><br /> <br><br /> <br>McVicker JK, Tatatabai LB. The isolation of immunogenic outer membrane proteins from Pasteurella (mannheimia) haemolytica A1 using selective extraction and immunoaffinity chromatography techniques. Am. J. Vet. Res. (in press).<br /> <br><br /> <br><br /> <br>Pillars RA, Grooms DL. Serological evaluation of five unvaccinated heifers for detecting herds persistently infected with bovine viral diarrhea virus, Am J Vet Res, 2002; 63: 499-5.<br /> <br><br /> <br><br /> <br>Ramirez-Romero R, Brogden KA, Gallup JM, Sonea IM, Ackermann, MR. Mast cell density and substance P-like immunoreactivity during the initiation and progression of lung lesions in ovine Mannheimia (Pasteurella) haemolytica pneumonia. Microb. Pathogen. 2001; 30; 325-335.<br /> <br><br /> <br><br /> <br>Vanden Bush TJ, RF Rosenbusch. 2002. Mycoplasma bovis induces apoptosis of bovine lymphocytes. FEMS Immunol. Med. Microbiol. 32: 97-103.<br /> <br><br /> <br><br /> <br>Walz PH, Bell TH, Wells J, Grooms DL, Kaiser L, Maes RK, Baker JC. Relationship between level of viremia and disease manifestations in calves experimentally infected with bovine viral diarrhea virus. Am J Vet Res, 2001; 62: 1095-1103.<br /> <br><br /> <br><br /> <br>Walz PH, Bell TH, Wells J, Grooms DL, Kaiser L, Maes RK, Baker JC. Platelet aggregation responses and virus isolation from platelets in calves experimentally infected with type I or type II bovine viral diarrhea virus. Can J Vet Res, 2001; 65:241-247.<br /> <br><br /> <br><br /> <br>Wang P, DJ Hurley LJ, Braun, CCL Chase. 2001. Detection of bovine herpesvirus 1 in peripheral blood mononuclear cells 8 months post infection. J. Vet. Diag. Invest, 13:424-427.<br /> <br><br /> <br><br /> <br>Ward ACS, Weiser GC, Delong WJ, Frank GH. Characterization of Pasteurella spp isolated from healthy domestic pack goats and evaluation of the effects of a commercial Pasteurella vaccine. Am. J. Vet. Res. 2002: 63: 119?123.<br /> <br><br /> <br><br /> <br>Winkler MTC, A Doster, J-H Sur, C Jones. 2002. Analysis of bovine trigeminal ganglia following infection with bovine herpesvirus 1. Vet. Microbiol. 86:139-155.<br /> <br><br /> <br><br /> <br>Wittum TE, Groteueschen DM, Brock KV, Kvasnicka WG, Floyd JG, Kelling CL, Odde KG. Persistent bovine viral diarrhea virus infection in U.S. beef herds. Vet Prev Med 2001;49:83-94.<br /> <br><br /> <br><br /> <br>Zhang Y, C Jones. 2001. The bovine herpes virus 1 immediate early protein (bICP0) is associated with histone deaetylase 1 to activate transcription. 2001. J. Virology 75:9571-9578.<br /> <br>

Impact Statements

1. OBJECTIVE 1 (Impact of Findings): Results document the pathogenetic synergy of bacterial and viral respiratory infections. BVDV isolates and their relationship to disease produced provides immunization targets. The IHC to identify PI calves is beneficial for the early elimination of this important virus reservoir. Serum Hp levels are of value to assess cattle that may become ill with respiratory disease and to monitor treatment efficacy. Comparison of genomic fingerprinting with other assays f
2. OBJECTIVE 2 (Impact of Findings): The pathogenesis of BHV-5 infection and the role of various BHV-5 gene products on neuro-invasiveness is more completely understood. Recognition of the increased production of LKT in low oxygen environments indicates that low oxygen tension in pneumonic tissue may be one host factor that predisposes to increased LKT production and greater severity of pneumonia. The dam gene is an important regulatory gene in the Pasteurellaceae and deletion or over-expression
3. OBJECTIVE 2 (Impact of Findings Continued): The results indicate that anti-cytokine therapy may represent a novel strategy for the management of bovine pneumonic Mannheimosis, and other diseases characterized by the overproduction of inflammatory cytokines. The IgBP may be an important component of future vaccine preparations. Absence of vhs activity should result in decreased pathogenicity and enhanced immunogenicity of BHV-1 vhs deletion mutant, making it a better vaccine candidate. The syne
4. OBJECTIVE 2 (Impact of Findings Continued): These studies will help understand bICP0 function and its relationship to disease and may help the vaccine industry design modified live vaccines that induce immunity, do not cause disease in cattle, and do not reactivate from latency. Understanding mechanisms of pathogeneses may help identify target areas for disease intervention.
5. OBJECTIVE 2 (Impact of Findings Continued): The results indicate that bovine CD18 is necessary and sufficient to mediate Lkt-induced cytolysis of target cells. The native and recombinant P. multocida 232 HasR has potential as an immunogen. Markers of genetic resistance to BRD would provide targets for research on control measures. A first description of a lymphotoxic activity of M. bovis is a landmark in the path towards characterization of virulence factors of the mycoplasma.
6. OBJECTIVE 3 (Impact of Findings): Another economical impact of BVDV persistent infection was demonstrated. Antiviral compounds may become useful in BRD treatment. The findings indicate the importance of aerosol exposure of the respiratory tract to immunogens of MH-1. Determination of recent exposure to MH-1 would direct preventive treatment regimens. Eliminating BVDV PI calves from the feedlot may reduce feedlot morbidity and increase performance, which is beneficial for economics and anim
7. OBJECTIVE 3 (Impact of Findings Continued): Mucosal exposure of calves to lktA- MH so that an immune response could develop before the calves were transported to a feedyard could offer protection from colonization and pneumonia caused by wild type MH. Fundamental molecular and cellular data on the role of defensins in innate-triggered adaptive immunity may prove useful for therapeutic applications for the prevention or treatment of BRD. The present findings add to the economic rationale for
8. OBJECTIVE 3 (Impact of Findings Continued): The results demonstrate that the more economical SC route of immunization is acceptable. Characterization of the immune response to M. bovis lung infection is important in establishing the type of vaccine that needs to be developed to elicit protection against M. bovis-induced BRD. Dual is a health management option that is available, affordable and effective, and may reduce antimicrobial resistance.

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Report Information

Participants

Briggs, Robert (bbriggs@nadc.ars.usda.gov) - USDA, ARS, National Animal Disease Center;
Brock, Kenny (brockkv@vetmed.auburn.edu) - Auburn U;
Chase, Chris (christopher_chase@sdstate.edu) - South Dakota State U;
Chowdhury, Shafiqul (chowdh@vet.k-state.edu) - Kansas State U;
Corstvet, Richard (rcorst1@lsu.edu) Louisiana State U;
Czuprynski, Chuck (czuprync@svm.vetmed.wisc.edu) - U of Wisconsin;
Fulton, Robert (rfulton@okstate.edu) - Oklahoma State U;
Gershwin, Laurel (ljgershwin@ucdavis.edu) - U of California, Davis;
Grooms, Dan (groomsd@cvm.msu.edu) - MI). Michigan State U;
Hurley, David (dhurley@vet.uga.edu) - U of Georgia;
Kousoulas, Konstantin (utgusk@lsu.edu) - Louisiana State U;
Lakritz, Jeff (lakritz.l@osu.edu)  Ohio State U;
Lawrence, Mark (lawrence@cvm.msstate.edu) - Mississippi State U;
Loan, Raymond (rloan@cvm.tamu.edu) - Texas A&M U;
Maheswaran, Sam (mahes001@tc.umn.edu) - U of Minnesota;
Miller, Jim (Jmillel@lsu.edu)  Louisiana State U;
Paulsen, Dan (dpaulsen@vetmed.lsu.edu)  Louisiana State U;
Rosenbusch, Ricardo (rfrosenb@iastate.edu) - Iowa State U;
Srikumaran, Sri (ssrikumaran1@unl.edu)  U of Nebraska;
Woolums, Amelia (awoolums@vet.uga.edu) - U of Georgia;

Brief Summary of Minutes

The annual meeting convened at 8 am on September 9, 2003. Welcome by Dr. Richard Corstvet and Dr. David Morison of Louisiana State University. Station reports began following the welcome and proceeded until 12 pm. The group broke for lunch from 12-1 pm. The business meeting was opened by chairperson Dr. Amelia Woolums (Georgia) at 1 pm. Minutes of the 2002 meeting, held in East Lansing, MI, were distributed earlier and following lack of comment from committee members, forwarded to the administrative advisor as being approved.



Dr. Woolums distributed notes from Dr. Eli Asem, committee administrative advisor, who was unable to attend meeting. Specific discussion was held on point #2 regarding The Ohio State University lack of a representative in NC 107. Dr. Jeff Lakritz has recently moved to OSU and would be an excellent station representative form OSU. The committee wishes that Dr. Asem communicate with OSU on making Dr. Lakritz the official station representative. With respect to point #3, Dr. Woolums asked that all representatives make sure that station reports include evidence of collaboration and impact summaries to aid Dr. Asem in writing the project interim report.



Dr. Woolums opened the floor for nominations for committee secretary for 2004. Dr. David Hurley (Georgia) was nominated by Dr. Sam Maheswaran and unanimously elected. Dr. Dan Grooms (Michigan) will ascend to committee chairperson in 2004.



Location for 2004 committee meeting was discussed and Dr. Sri Srikumaran volunteered Nebraska. Meeting date was set for September 14-15, 2004.



Future meeting locations were discussed and tentatively set as California in 2005 and Georgia in 2006.



Further discussion was held with regards to station representatives from states where currents representatives have left or are leaving soon. Replacements for Dr. Ray Loan (Texas), Dr. Jeff Lakritz (Missouri), Dr. Richard Corstvet (Louisiana) and Dr. Sreevatsan (Ohio) are needed. The committee asked that Dr. Asem contact the directors of these stations to begin the process of appointing new representatives. Suggested candidates included Wiske (Texas), Kleibocker and Larson (Missouri), Lakritz (Ohio) and Miller and Paulsen (Louisiana).



Discussion on meeting format was held. The committee consensus was the current format of individual station presenting relevant research is good and provides a catalyst for collaboration among participants. It was suggested by Ricardo Rosenbusch (Iowa) that we set aside some time next year to review progress on meeting current project objectives.



Dr. Woolums noted that compiled station reports were not mailed this year as has previously been done. Reports were distributed at the beginning of the meeting. This saved on postage and allowed for a more complete compilation of station reports (e.g. late station reports could be included in folders). Committee members agreed this format is fine and Grooms will follow this format in 2004.



Dr. Maheswaran noted his frustration that nobody from CSREES was present at the meeting. He noted that CSREES presence historically has provided an excellent source of information on funding.



Sri Srikumaran moved for a resolution of appreciation for Dr. Ray Loan (Texas) and his contributions to NC-107. Motion passed unanimously.



Sri Srikumaran moved for a resolution of appreciation for Dr. Richard Corstvet (Louisiana) and his contributions to NC-107. Motion passed unanimously.



An official welcome to new station representatives was directed towards Drs. Mark Lawrence (Mississippi) and Dr. Chowdhury (Kansas).



Chris Chase (South Dakota) moved to adjourn the meeting, 2nd by Sri Srikumaran.



Business meeting adjourned at 2 pm on September 8, 2003. Station reports resumed from 2 pm until 5 pm on September 9. The following morning, September 10, station reports resumed at 8 am. Meeting of the NC-107 Technical Committee was adjourned at 11pm on September 10, 2003



Assigned responsibilities: Dr. Woolums will prepare this years annual report and forward to Dr. Asem for submission as part of the mid-term review. Dr. Grooms (Chair for 2003-2004) will communicate with Dr. Srikumaran (in charge of local arrangements for the 2004 meeting) and Dr. Asem in coming months to distribute information regarding the next meeting. Dr. Grooms will distribute minutes and updated address list for group. Dr. David Hurley (GA) will serve as the Secretary for 2004 and Chair for 2005.



Next meeting information: September 14-15, 2004, at Nebraska. Dr. Srikumaran will coordinate local arrangements.









SUMMARY OF INTERDEPENDENCE AMONG MEMBERS OF NC-107 TECHNICAL COMMITTEE:



The members of the NC-107 technical committee are using a multi-disciplinary and a multi-state approach to gain knowledge about the causes of bovine respiratory disease and eventually develop solutions to the prevention, diagnoses, treatment and management of this disease. The hallmark of the research collaborations between members of NC-107 is that the interactions bring together scientists with skills in a variety of fields: for example, those who have skills in molecular biology, or microbiology, with those who have skills in pathology, or assessment of clinical disease. These collaborations allow a powerful multidisciplinary approach to solving the complex and multifactorial problem of bovine respiratory disease. Moreover, the annual meeting of the technical committee is perennially a site of lively, productive discussion that leads to the regular development of new research collaborations. The past history and ongoing activities of this group confirm that they will continue to interact in useful and productive ways that improve the ability of veterinarians and producers to minimize morbidity and mortality due to bovine respiratory disease. Members of the NC-107 Technical Committee display interdependence on a variety of levels. SHARING OF INFORMATION: Member stations collaborate by sharing information. For example, data regarding incidence of pathogens that cause bovine respiratory disease as reported by regional diagnostic laboratories is shared among members of the group. This information allows members to recognize new patterns of disease, or emerging diseases that contribute to bovine respiratory disease and thus are relevant to the research mission of the group. SHARING OF REAGENTS: Member stations collaborate in the sharing reagents and materials for research. For example, investigators in Iowa shared primer sequences with those in Georgia for the development of PCR assays for identification of mycoplasmas, and has also provided immunohistochemistry expertise. RESEARCH COLLABORATIONS: Members of the technical committee have been involved in productive research collaboration for many years; one of many examples includes the interactions between researchers at National Animal Disease Center (NADC) and Oklahoma to characterize respiratory disease that occurs in shipped, high-risk beef calves, and to document emerging agents that contribute disease in these calves. Another example is the interaction between investigators at Alabama and Michigan to determine the impact of inclusion of a calf persistently viremic with BVD in a group of shipped cattle on the incidence of respiratory disease in cattle in the group. COLLABORATIONS IN PUBLIC ENGAGEMENT: Member stations collaborate in educating veterinarians and producers. For example, in 2001 the group collaborated to present a symposium on bovine respiratory disease for the Academy of Veterinary Consultants, a leading organization of veterinary practitioners engaged in bovine practice.















ACTIVE EXTRAMURAL FUNDING OF NC-107 TECHNICAL COMMITTEE MEMBERS:



PI: Chowdhury S.

Agency: USDA/NRICGP.

Title: Role of glycoproteins gE and gI in BHV-1 and BHV-5 differential neuropathogenesis.

Duration: 10/1/2000 to 9/30/2004.

Amount: $ 285,000.





PI: Czuprynski CJ.

Agency: USDA/NRICGP.

Title: Role of purinergic receptors in endothelial cell damage by Haemophilus somnus.

Duration: 9/00 to 8/04.

Amount: $180,000.





PI: Maheshwaran S.

Agency: USDA/NRICGP.

Title: Characterization and role of Mannheimia haemolytica receptors.

Duration: 2000 to 2004.

Amount: $256,000.





PI: Maheshwaran S.

Agency: Minnesota Agricultural Experiment Station.

Title: Molecular characterization of Mannheimia haemolytica leukotoxin-LFA-1 interaction.

Duration: 2001 to 2004.

Amount: $90,000.





Investigators: Page, Todd, Czurynski CJ.

Agency: NIH.

Title: Caspase activation during PAH induced apoptosis.

Duration: 3/01 to 2/04.

Amount: $140,000.





PI: Rosenbusch, RF.

Agency: Boehringer Ingelheim Vetmedica.

Title: Extracts of Mycoplasma bovis as antigens for vaccines.

Duration: 10/2000 to 12/2003.

Amount: $178,594.





PI: Woolums AR.

Agency: USDA/NRICG.

Title: Multidisciplinary Evaluation of Fatal Feedlot ARDS.

Duration: 9/00 to 8/04.

Amount: $240,000

Accomplishments

OBJECTIVE 1: Identify emerging and re-emerging agents and develop diagnostic methods for bovine respiratory disease (BRD).<br /> <br><br /> <br>Georgia: In collaboration with IA, PCR and IFA assays are being developed to identify pathogenic bovine mycoplasma cattle. Mycoplasma sp. appears to be common but M. bovis to be less common. <br /> <br><br /> <br>Iowa: Since VspA antigen of Mycoplasma bovis was used as specific target for ELISA serology and immunohistochemistry (IHC). In 166 diagnostic accessions yielding M. bovis cultures, 15.9% of positive mastitis cases yielded cultures with VspA OFF (not expressed). The proportion of cases with VspA OFF among cases from beef cattle was 31.9%, and 45.5% from dairy calves. The high proportion of VspA OFF isolations suggests that ELISA serology based on VspA may not be a sensitive indicator of exposure to M. bovis.<br /> <br><br /> <br>Louisiana: Over 300 bovine coronavirus strains have been isolated from animals that experienced acute respiratory disease during two different shipping fever epizootics. Comparing the sequences of the enteric and lung genomes has revealed numerous single nucleotide substitutions.<br /> <br><br /> <br>Michigan: A rapid detection of BVDV in cell culture media using a biosensor was demonstrated. The results of other studies suggested that Johne&lsquo;s disease, characterized by positive M. paratuberculosis fecal culture or antibody ELISA test results, has no significant effect on the results of the CFT test for bovine tuberculosis in cattle. <br /> <br><br /> <br>Oklahoma: In collaboration with NADC, bovine viral diarrhea virus (BVDV) subtype 1b was shown to be transmitted to both vaccinated and non-vaccinated calves, including BVDV1b seronegative and seropositive calves, after exposure to persistently infected (PI) calves. An antigen capture ELISA (AC ELISA) test kit and a RT-PCR test were used to detect bovine coronavirus (BCV) in nasal swabs collected from four groups of cattle. The AC ELISA is a test with useful screening potential with ease of testing. The RT-PCR test, while requiring more equipment and technical skills, did identify more BCV positive cattle. <br /> <br><br /> <br>OBJECTIVE 2: Characterize mechanisms and intervention targets in pathogenesis of BRD at the molecular, cellular, and host level.<br /> <br><br /> <br>California: BRSV infected allergen (ovalbumin, OA) aerosol exposed calves, in general, had detectable OA specific IgE by day 10 and initial analysis of results show a correlation between IgE responsiveness and IL-4 producing T cells in lymph. <br /> <br><br /> <br>Georgia: Messenger RNA for IL-4 and IFN-gamma was measured using RT-cPCR of total RNA extracted from lung tissue and bronchoalveolar lavage fluid cells from calves experimentally challenged with BRSV. The results show that BRSV infection can induce a T helper type 1 response.<br /> <br><br /> <br>Iowa: Developed a serum-free, primary cell culture of bovine lung alveolar type 2 cells. Cultures were 80% positive for Nile Red incorporation into cytoplasmic lamellar bodies. Cultures of aortic endothelial cells were infected with an abscessing or a non-abscessing strain of Mycoplasma bovis. Cells were examined for ICAM-1 up-regulation, nitric oxide synthase activation, and VCAM-1 up-regulation. Up-regulation of VCAM-1 expression was the only signal detected.<br /> <br><br /> <br>Kansas: Investigated the role of BHV-5 gE cytoplasmic tail in the BHV-5 gE processing, envelope incorporation and neuropathogenesis. The data show that gE cytoplasmic domain is required for posttranslational modification of the gE. In other work, mouse strains that are deficient for TLR4 are susceptible to infection with substance P. pneumotropica and develop notable pulmonary lesions. However, reconstitution of TLR4-deficient mice with TLR4 positive macrophages derived from bone marrow or cultured cell lines results in subsequent resistance to experimental infection.<br /> <br><br /> <br>Minnesota: Studies examined the role of the major ligand-binding domain in LFA-1 in both binding to M. haemolytica LktA and mediating LktA-induced effects. The results demonstrated that the LktA binding domain is within the CD18 molecule. However, cellular activation upon LktA binding requires the interaction of CD18 and CD11a. Recently, this group has successfully cloned and sequenced the bovine CD11a coding sequence which has 81.6% nucleotide identity to human CD11a. <br /> <br><br /> <br>Mississippi: Research was undertaken to determine the role of DNA adenine methylase in virulence of P. These findings indicate that appropriate expression of Dam is required for virulence of P. multocida. <br /> <br><br /> <br>Missouri: Examined the role of host matrix degrading enzymes in the pathogenesis of BRD. Studies determined the expression of gelatinases in healthy calf lungs by examining MMP activity in bronchoalveolar lavage fluid from calves reared in the clinic. All calves possessed gelatinase activity as MMP 2 and MMP 9. Cell culture of alveolar macrophages, followed by stimulation with LPS, PMA, rbIL-1beta, rhTNFalpha, demonstrated expression of only MMP 9 in conjunction with other inflammatory mediators. <br /> <br><br /> <br>Nebraska: Demonstrated that heat shock protein gp96 peptide complexes isolated from a murine cell line transduced with glycoprotein D (gD) of BHV 1 induce CTLs specific for BHV 1 in mice. The feasibility of inducing CTL response against BHV 1 was examined, by co immunization with plasmids encoding BHV 1 gD (pELVSgD) and bovine gp96 (pS Btgp96). The group of mice co immunized with pELVSgD and pS Btgp96 developed a strong CTL response against BHV 1. However, the CTL response of mice co-immunized with pELVSgD and pS-Btgp96 was not higher than that of mice immunized with pELVSgD alone. Calves infected with the LR mutant exhibited mild clinical symptoms, but they sero converted. <br /> <br><br /> <br>Oklahoma: Isolated bovine neutrophils were used to study the relationship between the duration and magnitude of the M. haemolytica leukotoxin-induced increase in intracellular calcium levels and leukotriene B4 synthesis. The research confirmed that a high and sustained intracellular calcium concentration was necessary to stimulate production of leukotriene B4, which is believed to play an important role in the pathogenesis of pulmonary M. haemolytica infection. The gene for M. haemolytica outer membrane protein PlpE was cloned and expressed. Vaccination of cattle with 100 microg of rPlpE markedly enhanced resistance against experimental challenge with virulent M. haemolytica, and addition of rPlpE to a commercial M. haemolytica vaccine significantly enhanced protection afforded by the vaccine against experimental challenge. <br /> <br><br /> <br>South Dakota: BVDV strains that cause acute disease produce a soluble factor that down regulates un-infected macrophage functions and surface marker expression. These strains also produce factors that cause apoptosis of epithelial cells. Nitric oxide production was increased by NCP BVDV with LPS but when co-infection with bacteria or yeast was done NO was decreased. NO production was down regulated by CP BVDV. CP BVDV also down regulated NO production through a soluble factor. Depolymerization of the cytoskeleton (microtubules or actin) had a major effect on BHV-1 replication. BHV-1 infection of macrophages resulted in down regulation of MHC Class I and Class II and CD 11b, 11c and 14 and inhibition of macrophage functions (phagocytosis and microbiocidial activity). BHV-4 infection did not affect any macrophage function.<br /> <br><br /> <br>Wisconsin: Interaction of the leukotoxin (LKT) with LFA-1 was shown to be necessary for the previously described ability of cytokines to enhance LKT cytotoxicity. Active BHV-1 infection was shown to alter responsiveness of bovine leukocytes to LKT; exposure to BHV-1 increased toxicity of LKT by increasing expression of LFA-1. In collaboration with MN, it was shown that preincubation of bovine PMNs with LKT or LPS enhanced cytotoxic activity of LKT. H. somnus and its LOS were shown to cause activation of bovine platelets and upregulation of surface molecules that may contribute to the development of vasculitis and thrombosis seen in H. somnus infection. <br /> <br><br /> <br>OBJECTIVE 3: Develop intervention strategies for critical control points to reduce the impact of BRD.<br /> <br><br /> <br>California: In a study to find an effective vaccine for BRSV that would stimulate a cell-mediated immune response without inducing disease enhancement, results show that the cDNA vaccine containing the BRSV NP protein provided some degree of protection, and appeared to induce the greatest proliferation of peripheral blood lymphocytes after vaccination and during infection. <br /> <br><br /> <br>Iowa: In vitro activation of bovine gamma-delta-T cells was observed to occur when stimulated with heated M. bovis antigen. PBMCs from infected or non-infected cattle yielded these cells, indicating that the reactivity was associated with innate immune responses.<br /> <br><br /> <br>Louisiana: Transfecting the upper respiratory tract of cattle with a gene coding for cecropin B does not result in a change in the indigenous and transient nasal flora. Results indicate that transfecting the upper respiratory tract with 100 microg of DNA per nostril does inhibit colonization of a virulent strain of M. haemolytica 1:A.<br /> <br><br /> <br>Michigan: In collaboration with AL, a study was undertaken to determine the effect that the continuous presence of PI cattle has on the overall performance of non-PI feedlot cattle. The results suggest that calves persistently infected with BVDV impact the performance of cohort feedlot cattle by increasing morbidity and decreasing average daily gain. <br /> <br><br /> <br>NADC: In collaboration with OK, a field trial was conducted on fall-shipped beef calves to evaluate a single-dose combination M. haemolytica/P. multocida edible modified-live vaccine formulation. The results indicated that vaccination with a modified-live M. haemolytica/P. multocida product single-dose product top-dressed on feed improved weight-gain of calves over a 35 day feeding trial by 6.1 kg compared to unvaccinated ones. <br /> <br><br /> <br>Oklahoma: The passive immunity transferred to calves from their dams was investigated in a beef herd. The mean half-life of viral antibodies was greater for vaccinates for all viruses, except BRSV. Mean antibody titers of vaccinates at day 116 were statistically higher than nonvaccinates for all viruses except BRSV. A study was undertaken to evaluate health status at entry to a feedlot against feedlot performance and carcass value. There were increased numbers of treatments for the individual animals in calves with low antibody levels of M. haemolytica whole cell antigen (MHWC), MH leukotoxin, BVDV1, BVDV2 and PI-3V. Seronegative persistently infected (PI) calves with bovine viral diarrhea virus (BVDV) subtype 1b were vaccinated with each of four modified live virus (MLV) BVDV vaccines and a M. haemolytica bacterin-toxoid. None of the PI calves developed mucosal disease (MD) after MLV vaccination. None of the BVDV PI calves seroconverted to BVDV1b after MLV vaccination. Calves receiving MLV vaccines seroconverted to the respective type/subtype in the vaccine. The PI BVDV1b calves did not respond with increased M. haemolytica antibodies after vaccination compared to BVDV negative calves receiving the same M. haemolytica vaccine.<br /> <br><br /> <br>South Dakota: A study was done to compare the effect of two dairy cow vaccination programs with either an inactivated vaccine in the dry period vs. MLV in the fresh period. There was no difference in production parameters with the exception of somatic cell count that was higher in MLV animals. Cows vaccinated with IV during the dry period had higher humoral and cellular response compared to cows vaccinated with a MLV.<br /> <br><br /> <br>Texas: Serum total antioxidant capacity (TACA) and serum malondialdehydes (MDA) were measured in transported cattle. Transportation stress decreased serum TACA and increased serum MDA.<br /> <br><br /> <br>NOTE: SEE THE "MINUTES" FOR DESCRIPTIONS OF INTERDEPENCENCE AMONG PARICIPATING MEMBERS AS WELL AS EXTRAMURAL FUNDING INFORMATION.

Publications

Carter JN, Meredith GL, Montelongo M, Gill DR, Krehbiel CR, Payton ME, Confer AW. Relationship of vitamin E supplementation and antimicrobial treatment with acute-phase protein responses in cattle affected by naturally acquired respiratory tract disease. Am J Vet Res 63:1111-1117, 2002.<br /> <br><br /> <br><br /> <br>Caverly JM, Diamond G, Gallup JM, Brogden KA, Dixon RA, Ackermann MR. Coordinated expression of tracheal antimicrobial peptide and inflammatory-response elements in the lungs of neonatal calves with acute bacterial pneumonia.<br /> <br>Infect Immun. 2003 May;71(5):2950-5.<br /> <br><br /> <br><br /> <br>Chen, L., D. B. Paulsen, D. W. Scruggs, M. M. Banes, B. Y. Reeks, and M. L. Lawrence.<br /> <br>2003. Alteration of DNA adenine methylase (Dam) activity in Pasteurella multocida<br /> <br>causes increased spontaneous mutation frequency and attenuation in mice. Microbiology. <br /> <br>In press.<br /> <br><br /> <br><br /> <br>Chase CCL, SK Chase and L Fawcett. 2003. Trends in the BVDV Serological Response in the United States Upper Midwest Region. Biologicals 31:145-151.<br /> <br><br /> <br><br /> <br>Chirase NK, Purdy CW, Avampato JM. Effect of simulated ambient particulate matter exposure on performance, rectal temperature and leukocytosis of young Spanish goats with or without tilmicosin phosphate. J An Sci. Accepted May 2003.<br /> <br><br /> <br><br /> <br>Cudd LA, Clarke CR, Clinkenbeard KD. Mannheimia haemolytica leukotoxin-induced increase in leukotriene B4 production by bovine neutrophils is mediated by sustained and excessive increase in intracellular calcium concentration. Accepted for publication by FEMS Micro. Let.<br /> <br><br /> <br><br /> <br>Confer AW, Ayalew S, Montelongo M, Panciera RJ, Whitworth LC, Hammer, JD. Immunogenicity of Mannheimia haemolytica serotype 1 recombinant outer membrane protein PlpE and augmentation of a commercial vaccine. Vaccine 21: 2821-2829: 2003<br /> <br><br /> <br><br /> <br>Dabo SM, Confer AW, Quijano-Blas RA. Molecular and immunological characterization of Pasteurella multocida A:3 OmpA: Evidence of its role in P. multocida interaction with extracellular matrix molecules. Microb Pathog, in press<br /> <br><br /> <br><br /> <br>S.M. Dabo, A.W. Confer, and R.A. Quijano-Blas: Department of Veterinary Pathobiology, Oklahoma State University, Stillwater, OK 74078-2007. Molecular and immunological characterization of Pasteurella multocida serotype A:3 OmpA: Evidence of its role in P. multocida interaction with extracellular matrix molecules. Bacterial Pathogenesis, in press, 2003.<br /> <br><br /> <br><br /> <br>Deshpande, M., T.C. Ambagala, A.P.N., Ambagala, and S. Srikumaran. 2002. Bovine CD18 is necessary and sufficient to mediate Mannheimia (Pasteurella) haemolytica leukotoxin induced cytolysis. Infection and Immunity, 70:5058 5064.<br /> <br><br /> <br><br /> <br>Fairbanks K, J Schnackel, and CCL Chase. 2003. Evaluation of a modified live virus type 1a bovine virus diarrhea vaccine (Singer strain) against a type 2 890 (Strain 890) challenge. Vet.Therapeutics 4:24-34.<br /> <br><br /> <br><br /> <br>Evermann JF, Ridpath JF. Clinical and epidemiologic observations of bovine viral diarrhea virus in the northwestern United States. Vet Microbiol. 2002 Oct 22;89(2-3):129-39.<br /> <br><br /> <br><br /> <br>Fajt VR, Apley MD, Roth JA, Frank DE, Brogden KA, Skogerboe TL, Shostrom VK, Chin YL. The effects of danofloxacin and tilmicosin on neutrophil function and lung consolidation in beef heifer calves with induced Pasteurella (Mannheimia) haemolytica pneumonia. J Vet Pharmacol Ther. 2003 Jun;26(3):173-9.<br /> <br><br /> <br><br /> <br>Frank GH, Briggs RE, Duff GC, Hurd HS. Effect of intranasal exposure to leukotoxin-deficient Mannheimia haemolytica at the time of arrival at the feedyard on subsequent isolation of M haemolytica from nasal secretions of calves. Am J Vet Res. 2003 May;64(5):580-5. <br /> <br><br /> <br><br /> <br>Fulton RW, Step DL, Ridpath JF, Saliki JT, Confer AW, Johnson BJ, Briggs RE, Hawley RV, Burge LJ, Payton ME. Response of calves persistently infected with noncytopathic bovine viral diarrhea virus (BVDV) subtype 1b after vaccination with heterologous BVDV strains in modified live virus vaccines and Mannheimia haemolytica bacterin-toxoid. Vaccine. 2003 Jun 20;21(21-22):2980-5. <br /> <br><br /> <br><br /> <br>Fulton RW, Ridpath JF, Confer AW, Saliki JT, Burge LG, Payton ME. Bovine viral diarrhoea virus antigenic diversity: impact on disease and vaccination programmes. Biologicals. 2003 Jun;31(2):89-95.<br /> <br><br /> <br><br /> <br>Fulton, R.W., Saliki, J.T., Burge, L.J., and Payton, M.: Humoral Immune Response and Assessment of Vaccine Virus Shedding in Calves Receiving Modified Live Virus Vaccines Containing Bovine Herpesvirus-1 and Bovine Viral Diarrhea Virus 1a. Journal of Veterinary Medicine B, 50:31-37, 2003.<br /> <br><br /> <br><br /> <br>Fulton, R.W., Ridpath, J.F., Confer, A.W., Saliki, J.T., Burge, L.J., and Payton, M.E.: Bovine Viral Diarrhoea Virus Antigenic Diversity: Impact on Disease and Vaccination Programmes. Biologicals, 31:89-95, 2003.<br /> <br><br /> <br><br /> <br>Fulton, R.W., Step, D.L., Ridpath, J.F., Saliki, J.T., Confer, A.W., Johnson, B.J., Briggs, R.E., Hawley, R.V., Burge, L.J., and Payton, M.E.: Response of Calves Persistently Infected with Noncytopathic Bovine Viral Diarrhea Virus (BVDV) Subtype 1 b after Vaccination with Heterologous BVDV Strains in Modified Live Virus Vaccines and Mannheimia haemolytica Bacterin-Toxoid. Vaccine, 21:2980-2985, 2003.<br /> <br><br /> <br><br /> <br>Gatto NT, Dabo SM, Hancock RE, Confer AW. Characterization of, and immune responses of mice to, the purified OmpA-equivalent outer membrane protein of Pasteurella multocida serotype A:3 (Omp28),. Vet Microbiol 87: 221-235, 2002<br /> <br><br /> <br><br /> <br>Geiser, G., Melissa Inman, Y. Zhang, and C. Jones. 2002. The latency related (LR) gene of bovine herpes virus 1 (BHV 1) can inhibit the ability of bICP0 to activate productive infection. J. of General Virology 83: 2965 2971.<br /> <br><br /> <br><br /> <br>Geiser, G., M. Inman, Y. Zhang, and C. Jones. 2002. The latency related (LR) gene of bovine herpes virus 1 (BHV 1) can inhibit the ability of bICP0 to activate productive infection. J. of General Virology 83: 2965 2971.<br /> <br><br /> <br><br /> <br>Geiser, V. and C. Jones. 2003. Stimulation of bovine herpesvirus 1 productive infection by the adenovirus E1A gene and the cellular transcription factor E2F4. J. of General Virology, 84:929 938.<br /> <br><br /> <br><br /> <br>Gopinath,R.S., A.P.N., Ambagala, S. Hinkley, and S. Srikumaran. 2002. Effects of virion host shut off activity of bovine herpesvirus 1 on MHC class I expression. Viral Immunology, 15: 595 608.<br /> <br><br /> <br><br /> <br>Grooms DL, Keilan E. Screening of neonatal calves for bovine viral diarrhea virus by immunohistochemistry on skin samples. Clin Diagn Lab Immun, 2002;9(4):898-9.<br /> <br><br /> <br><br /> <br>Harding, M. J., X. Cao, H. Shams, A.F. Johnson, V.B. Vassilev, L.H., D.W. Wheeler, D. Haines, G.J. Sibert, L.D. Nelson, M. Campos, M., R.O. Donis. (2002). Role of bovine viral diarrhea virus biotype in the establishment of fetal infections. Am J Vet Res 63(10), 1455 63.<br /> <br><br /> <br><br /> <br>Inman, M., L. lovato, A. doster, and C. jones. 2002. A mutation in the latency related gene of bovine herpesvirus 1 disrupts the latency reactivation cycle in calves. J. of Virology, 76:6771 6779.<br /> <br><br /> <br><br /> <br>Jeyaseelan, S., S. Srinand, and S.K.Maheswaran. 2002. Role of Mannheimia haemolytica leukotoxin in the pathogenesis of bovine pneumonic pasteurellosis. Animal Health Research Reviews. 3: 69-82.<br /> <br><br /> <br><br /> <br>Jones, C. Analysis of HSV 1 and BHV 1 1 latency. 2003. Clinical Microbiology Reviews. 16:79 95<br /> <br><br /> <br><br /> <br>Kelling, C.L., Steffen, D.J., Topliff, C.L., Eskridge, K.M., Donis, R.O., Higuchi, D.S. 2002. Comparative virulence of bovine viral diarrhea virus type II in experimentally inoculated six to nine month old calves. American Journal of Veterinary Research 63:1379 1384.<br /> <br><br /> <br><br /> <br>Kelling, C.L., D. J Steffen, V.L Cooper, D.S. Higuchi, K.M. Eskridge. 2002. Effect of acute bovine viral diarrhea virus alone, bovine rotavirus alone, or concurrent infection with both on enteric disease in gnotobiotic neonatal calves. American Journal of Veterinary Research. 63:1179 1186.<br /> <br><br /> <br><br /> <br>Lakritz J, Marsh AE, Cockrell M, Smith MF, Tyler JW. Characterization of gelatinases in bronchoalveolar lavage fluid and produced by alveolar macrophages isolated from healthy calves. Accepted, July 10, 2003; Am. J. Vet. Res. <br /> <br><br /> <br><br /> <br>Liang, D., I.F. Sainz, I.H. Ansari, L.H. Gil, V. Vassilev, and R.O. Donis (2003). The envelope glycoprotein E2 is a determinant of cell culture tropism in ruminant pestiviruses. J Gen Virol 84(Pt 5), 1269 74.<br /> <br><br /> <br><br /> <br>Leite FS, O!&Brien MJ, Sylte, et al. 2002. Inflammatory cytokines enhance the interaction of Mannheimia haemolytica leukotoxin with bovine peripheral blood neutrophils in vitro. Infect Immun 70:4336-4343.<br /> <br><br /> <br><br /> <br>Leite FS, Giles D, Atapattu, et al. 2003. Prior exposure to Mannheimia haemoloytica leukotoxin or LPS enhances Beta2-integrin expression by bovine neutrophils and augments leukotoxin cytotoxicity. Microb Pathogen 34:267-275.<br /> <br><br /> <br><br /> <br>Liebler-Tenorio EM, Ridpath JF, Neill JD. Lesions and tissue distribution of viral antigen in severe acute versus subclinical acute infection with BVDV2.<br /> <br>Biologicals. 2003 Jun;31(2):119-22. <br /> <br><br /> <br><br /> <br>Liebler-Tenorio EM, Ridpath JF, Neill JD. Distribution of viral antigen and development of lesions after experimental infection of calves with a BVDV 2 strain of low virulence. J Vet Diagn Invest. 2003 May;15(3):221-32.<br /> <br><br /> <br><br /> <br>Lovato, L., M. Inman, G. Henderson, A. Doster., and C. Jones, C. 2003. Infection of cattle with a bovine herpesvirus 1 (BHV 1) strain that contains a mutation in the latency related gene leads to increased apoptosis in trigeminal ganglia during the transition from acute infection to latency. J of Virology, 77:4848 4857.<br /> <br><br /> <br><br /> <br>Maheswaran, S.K., P. Thumbikat, and T. Dileepan. 2002. Current knowledge on pathogenesis of lung injury caused by Mannheimia haemolytica and Pasteurella multocida in the bovine. Recent Developments and Perspectives in Bovine Medicine. Pages 160-167.<br /> <br><br /> <br><br /> <br>Mott, K., N. Osorio, L. Jin, D. Brick, J. Naito, J. Cooper, G. Henderson, M. Inman, C. Jones, S. L. Wechsler, and G. C. Perng. 2003. The BHV 1 LR gene!&s ability to restore the high reactivation phenotype to an HSV 1 LAT null mutant appears to be due to its anti apoptosis function. Journal of General Virology, IN PRESS.<br /> <br><br /> <br><br /> <br>Pillars RA, Grooms DL. Serological evaluation of five unvaccinated heifers for detecting herds persistently infected with bovine viral diarrhea virus, Am J Vet Res, 2002;63(4):499-5.<br /> <br><br /> <br><br /> <br>Purdy CW, Straus DC, Chirase N, Ayers JR, Hoover MD. Effects of aerosolized dust in goats on lung clearance of Pasteurella and Mannheimia species. Curr Micro 46(3):174. 2003.<br /> <br><br /> <br><br /> <br>Risatti, G. R., D. Pomp, and R.O. Donis (2003). Patterns of cellular gene expression in cells infected with cytopathic or non cytopathic bovine viral diarrhea Virus. Animal Biotechnology 14(1), 31 49.<br /> <br><br /> <br><br /> <br>Sylte MJ, Leite FP, Kuckleburg, Et al. 2003. Haemophilus somnus lipooligosaccharide-mediated apoptosis of bovine endothelial cells is caspase-8 dependent. Microb Pathogen. In press.<br /> <br><br /> <br><br /> <br>Thumbikat, P., R.E. Briggs, M.S. Kannan, and S.K. Maheswaran. 2003. Biological effects of two genetically defined mutants of Mannheimia haemolytica. Microb. Pathog. 34: 217-226.<br /> <br><br /> <br><br /> <br>Thumbikat P, Briggs RE, Kannan MS, Maheswaran SK. Biological effects of two genetically defined leukotoxin mutants of Mannheimia haemolytica. Microb Pathog. 2003 May;34(5):217-26.<br /> <br><br /> <br><br /> <br>Vanden Bush T. J., and R. F. Rosenbusch. 2003. Characterization of the immune response to Mycoplasma bovis lung infection. Vet. Immunol. Immunopath. 94: 23-33.<br /> <br><br /> <br><br /> <br>Woolums AR, Brown C, Brown Jr JC, et al. Effects of a single intranasal dose of modified-live bovine respiratory syncytial virus vaccine on resistance to subsequent viral challenge in calves. Am J Vet Res. In press. 2003.<br /> <br><br /> <br><br /> <br>Woolums AR, Siger S, Johnson S, Gallo G, Conlon J. Rapid onset of protection following<br /> <br>vaccination of calves with multivalent vaccines containing modified-live or modified-live<br /> <br>and killed BHV-1 is associated with virus-specific interferon gamma production. Vaccine. <br /> <br>2003; 21: 1158-1164.<br /> <br><br /> <br><br /> <br>Purdy CW, Straus DC, Chirase N, Parker DB, Ayers JR, Hoover MD. Effects of aerosolized endotoxin in feedyard dust on weanling goats. Small Rum Res 446:133. 2002.<br /> <br> <br /> <br><br /> <br>ABSTRACTS:<br /> <br><br /> <br>Blackwood ER, Ayalew S, Confer AW. Molecular and Immunological Analysis of Outer Membrane Protein PlpE from Mannheimia haemolytica serotypes 1, 2, and 6. 83th Annual Meeting of CRWAD, 93, St. Louis, MO, 2002.<br /> <br><br /> <br><br /> <br>Bolin SR. BVD: The old and the new. Proceedings of the Minnesota Dairy Health Conference, St. Paul Minnesota, May20, 2003. pp 14-17.<br /> <br><br /> <br><br /> <br>Brady, R.P., C.L. Topliff, C.L. Kelling. 2002. Analyses of plasmid DNA encoding the attachment glycoprotein of bovine respiratory syncytial virus. Conference of Research Workers in Animal Diseases Proceedings. <br /> <br><br /> <br><br /> <br>Braun, LJ, M Braunschmidt, N Arias, Regina Wixon, CY Wang and CCL Chase. Effect of genistein on bovine herpesvirus 1 and bovine viral diarrhea virus infections in vivo. 35th annual Conference of American Association of Bovine Practitioners, Rapid City, SD, September 26-28, 2002, p. 206. <br /> <br><br /> <br><br /> <br>Chase CCL, G Elmowalid and LJ Braun. Effect of bovine viral diarrhea virus on bovine macrophages inflammatory functions and surface marker expression in vitro. Abstract A-4. 9th National Symposium: Basic Aspects of Vaccines, Bethesda, MD, April 30-May 2, 2003.<br /> <br><br /> <br><br /> <br>Confer AW. Pathogenesis of Bovine Bacterial Pneumonia. Proceedings ACVIM Forum, Charlotte, NC. 2003<br /> <br><br /> <br><br /> <br>Confer AW. Appropriate Usage of Antibiotics for Disease Control. Proceedings 2003 ASAS/ADSA Midwestern Regional Meeting, Des Moines, IA, 2003<br /> <br><br /> <br><br /> <br>Dabo SM, Confer AW, Quijano-Blast, RA. Pasteurella multocida OmpA as a potential adherence factor. Proceedings 103rd Annual Meeting of American Society of Microbiology, Washington, DC. 2003<br /> <br><br /> <br><br /> <br>Dabo SM, Confer AW, Quijano-Blast, RA. Identification of Bartonella henselae fibronectin binding proteins. Proceedings 103rd Annual Meeting of American Society of Microbiology, Washington, DC. 2003<br /> <br><br /> <br><br /> <br>Dunn J, Kaneene JB, Grooms D, Bolin S, Bolin C, Bruning-Fann C. The effect of infection with Mycobacterium paratuberculosis on the reliability of the caudal fold tuberculin (CFT) test and the gamma-interferon test for bovine tuberculosis in cattle. Proceedings of the 83th Annual Meeting of The Conference of Research Workers in Animal Diseases, St. Louis, MO, November 11, 2002. Abstract # 47.<br /> <br><br /> <br><br /> <br>Elmowalid, G, BL Ransom, LJ Braun, A Young, J Ridpath and CCL Chase. Bovine viral diarrhea virus interferes with macrophage surface marker expression in vitro. Abstract 185. 83rd annual meeting of Conference of Research Workers in Animal Disease, St. Louis, MO, November 11-12, 2002.<br /> <br><br /> <br><br /> <br>Fulton, R.W., Step, D.L., Ridpath, J.F., Saliki, J.T., Confer, A.W., Johnson, B.J., Welsh, R.D., Burge, L.J., Hawley, R.V., and Payton, M.E.: Bovine Viral Diarrhea Virus (BVDV) Persistently Infected Calves: Response to Vaccinations and Diagnoses at Necropsy. 45th Annual Meeting of AAVLD, October 18-22, 2002. St. Louis, MO.<br /> <br><br /> <br><br /> <br>Fulton, R.W., Step, D.L., Ridpath, J.F., Saliki, J.T., Confer, A.W., Johnson, B.J., Welsh, R.D., Burge, L.J., Hawley, R.V., and Payton, M.E.: Bovine Viral Diarrhea Virus (BVDV) Infections of Calves after Exposure to Persistently Infected Calves with BVDV Subtype 1b. 45th Annual Meeting of AAVLD. October 18-22, 2002. St. Louis, MO.<br /> <br><br /> <br><br /> <br>Gopinath, R.S., T.C. Ambagala, A.P.N. Ambagala and S. Srikumaran. GP96 as an adjuvant for the induction of cytotoxic T lymphocytes (CTLs) specific for bovine herpesvirus 1 (BHV 1). International Herpesvirus Workshop. July 26 31, 2003. <br /> <br><br /> <br><br /> <br>Grooms DL, Brock KV, Norby B. Performance Of Feedlot Cattle Exposed To Animals Persistently Infected With Bovine Viral Diarrhea Virus. Proceedings of the 83th Annual Meeting of The Conference of Research Workers in Animal Diseases, St. Louis, MO, November 11, 2002. Abstract # 186<br /> <br><br /> <br><br /> <br>Hassan EAD, B Tigabu, LJ Braun and CCL Chase. Reorganization of microtubules and actin filaments in bovine herpesvirus-1-infected cells and their role in virion egress. Abstract p28-5. 22nd Annual Meeting of American Society for Virology, Davis, CA July 12-16, 2003.<br /> <br><br /> <br><br /> <br>Hassan, EAD, LJ Braun, and CCL Chase. The effect of bovine herpesvirus 1 (BHV-1) on the organization of actin filaments and microtubules. Abstract 116-P. 83rd annual meeting of Conference of Research Workers in Animal Disease, St. Louis, MO, November 11-12, 2002. <br /> <br><br /> <br><br /> <br>Hunsaker, B.D, C.L.Topliff, J.A. Achenbach, C.L.Kelling. 2002. Back passage of a commercial modified live vaccine (MLV) strain of type 1 noncytopathic bovine viral diarrhea virus did not result in reversion to virulence. Conference of Research Workers in Animal Diseases Proceedings.<br /> <br><br /> <br><br /> <br>Inman, M. and C. Jones, Identification and Characterization of a Novel Transcript containing an ORF that is expressed during latency, and is Antisense to the Latency Related Gene of BHV 1. International Herpesvirus Workshop. July 26 31, 2003.<br /> <br><br /> <br><br /> <br>Jiang, Y., M. Inman, Y. Zhang, and C. Jones. A mutation in the latency related gene of bovine herpesvirus 1 (BHV 1) inhibits expression of proteins encoded by ORF2 and Reading Frame C during productive infection. International Herpesvirus Workshop. July 26 31, 2003.<br /> <br><br /> <br><br /> <br>Lasarsky, E., Fulton, R.W., Confer, A.W., Saliki, J.T., Briggs, R.E., and Huchzermeier, R.: Bovine Coronavirus Infections in Cattle: Detection in Nasal Swabs by Antigen Capture ELISA and RT-PCR. CRWAD, November 10-12, 2002. St. Louis, MO.<br /> <br><br /> <br><br /> <br>Lin, K-f, McArthur-Vaughan, K., Rhodes, G.H., Gershwin, L.J. Evaluation of cDNA Vaccines Coding for F or N Proteins of Bovine Respiratory Syncytial Virus: Clinical Outcome and Immune Response. W43-12. American Society for Virology, 22nd Annual meeting, University of California, Davis. July 12-16, 2003.<br /> <br><br /> <br><br /> <br>Lu, X., and R. F. Rosenbusch. Mycoplasma bovis induces the up-regulation of VCAM-1 and ICAM-1 in bovine aortic endothelial cells. 83rd Annual Meeting of the Conference for Research Workers in Animal Disease, St. Louis, Poster 6P, 2002.<br /> <br><br /> <br><br /> <br>Maheswaran, S. K., C. Malazdrewich, and H.S. Yoo. 2002. The role of proinflammatory cytokines TNF-alpha, IL-1-beta, and IL-8 in pneumonic mannheimiosis. Proceedings 8th International Vet. Emergency and Critical Care Symposium, Pp 423-426. September 4-8, <br /> <br>San Antonio, Texas.<br /> <br><br /> <br><br /> <br>Maheswaran, S.K., and P. Thumbikat. 2002. Molecular characterization of the Mannheimia haemolytica leukotoxin receptor: Controversy and conundrums. Proc. 83rd Conf.Res. Workers Anim. Dis. Abst. No: 1.<br /> <br><br /> <br><br /> <br>Marsh, T and C Chase. Evaluation of alternate year vaccination practices in a cow-calf herd. 35th annual conference of American Association of Bovine Practitioners, Rapid City, SD, September 26-28, 2002, p. 172.<br /> <br><br /> <br><br /> <br>Miao C, Woolums AR, Brown C, Brown C, Brown Jr JC, Williams S, Zarlenga DS. Measurement of cytokine gene expression by RT-competitive PCR in BRSV vaccinated and infected calves. Proceedings of the Conference for Research Workers in Animal Disease (CRWAD), St. Louis MO, November 2002. <br /> <br><br /> <br><br /> <br>Mott, K.R., N. Osorio, L. Jin, D. Brick, J. Naito, J. Cooper, G. Henderson, M. Inman, C. Jones, S. L. Wechsler, and G. C. Perng. The BHV 1 LR gene&lsquo;s ability to restore the high reactivation phenotype to an HSV 1 LAT null mutant appears to be due to its anti apoptosis function. ARVO meeting (vision and ophthalmology meeting), May, 2003.<br /> <br><br /> <br><br /> <br>Prado ME, Dabo SM, Confer AW. Cloning and characterization of HasR gene homologue from Pasteurella multocida A:3. Proceedings of HAP2002, Banff, Alberta, Canada, 2002.<br /> <br><br /> <br><br /> <br>Thumbikat, P., T. Dileepan, and S.K. Maheswaran. 2003. The bovine LFA-1 domain plays a critical role in mediating target cell activation but not binding of Mannheimia haemolytica leukotoxin. 103rd General Meeting, American Society Microbiology, Abstract # E-101.<br /> <br><br /> <br><br /> <br>Topliff, C.L., S.K.Chon, R.O. Donis, K.M. Eskridge, C.L.Kelling. 2002. Translational Efficiencies of genotype 2 bovine viral diarrrhea virus field isolates using a T7 vaccinia virus expression system. Conference of Research Workers in Animal Diseases Proceedings.<br /> <br><br /> <br><br /> <br>Y. Zhang & C. Jones. The bovine herpes virus 1 (BHV 1) immediate early gene encodes a protein (bICP0) that inhibits p53 transcriptional activity by sequestering A histone acetyltransferase (p300). International Herpesvirus Workshop. July 26 31, 2003.<br /> <br><br /> <br><br /> <br> <br /> <br><br /> <br>DISSERTATION AND THESES:<br /> <br><br /> <br>Elmowalid, Gamal. Unmasking the effect of bovine viral diarrhea virus on macrophage inflammatory functions. PhD Dissertation, South Dakota State University, 2002.<br /> <br><br /> <br><br /> <br>Arias, Nicolas. Analysis of Two Vaccination Programs in Dairy Cows and Their Impact on the Herd Performance and Colostrum Quality. Master of Science Thesis, South Dakota State University, 2003.<br /> <br><br /> <br><br /> <br>Miao, Congrong. Cytokine messenger RNA expression in calves vaccinated intranasally with modified-live bovine respiratory syncytial virus (BRSV) prior to BRSV challenge. Master of Science Thesis, University of Georgia, 2003.<br /> <br><br /> <br><br /> <br>Ransom, Brian. The Effect of Bovine Herpesvirus Type 1 or Type 4 on the Functional Characteristics of Monocyte-Derived Macrophages. Master of Science Thesis, South Dakota State University, 2003.

Impact Statements

1. OBJECTIVE 1 (Impact of Findings): Georgia: Assays being developed will allow identification of pathogenic mycoplasma, which will help determine whether specific types of operations are at greater risk for disease. Assays will be useful in studies to determine risk factors for respiratory disease due to pathogenic mycoplasma.
2. OBJECTIVE 1 (Impact of Findings Continued): Iowa: An ELISA test usable to detect sero-responses to M. bovis infections is needed. This survey study of expression of VspA in field cases indicates that prominent variable surface proteins may not be good targets for use in ELISA, giving problems in sensitivity even while providing adequate specificity. Use of a pool of reagents with differing specificity is recommended for IHC diagnosis.
3. OBJECTIVE 1 (Impact of Findings Continued): Louisiana: Bovine coronaviruses are involved in bovine respiratory and enteric tract diseases that cause important economic losses in animal agriculture. Characterization of respiratory bovine coronaviruses involved in upper respiratory disease and fatal pneumonia will lead to a greater understanding of the organisms role in BRD.
4. OBJECTIVE 1 (Impact of Findings Continued): Michigan: Further development of the BVDV biosensor may make this a useful tool for the rapid and economical identification of PI cattle. Veterinarians should be aware that a high number of CFT suspects do not necessarily correlate with a high prevalence of Johnes disease in a herd. Research should continue for in vitro methods of diagnosing TB that compare M. bovis to M. avium and M. paratuberculosis during the first round of testing.
5. OBJECTIVE 1 (Impact of Findings Continued): Michigan: Information derived from the study of the effect of vaccination for respiratory viruses on the response to TB testing will be useful in improving the accuracy of whole herd TB testing currently being use in Michigan and other states where bovine TB has reemerged.
6. Impact 6: OBJECTIVE 2 (Impact of Findings): California: Control of BRSV infection may mitigate lung effects of allergen exposure in cattle. BRSV/H. somnus studies have revealed aspects of the pathogenesis of co-infection with these two pathogens that were previously unknown; control of T helper cell responses could impact outcome of co-infection
7. Impact 7: OBJECTIVE 2 (Impact of Findings Continued): Georgia: T helper cell cytokines could be related to differences in individual responses to BRSV infection; modulation of T cell responses could impact disease outcome in BRSV infection
8. Impact 8: OBJECTIVE 2 (Impact of Findings Continued): Iowa: Availability of cultured cells of bovine alveolar type 2 phenotype will provide an important new in-vitro tool to study the pathogenesis of bovine respiratory disease
9. Impact 9: OBJECTIVE 2 (Impact of Findings Continued): Kansas: These studies have helped define the comparative pathogenesis of neurovirulent (BHV-5) and non-neurovirulent (BHV-1) bovine herpesviruses. Substance P and TLR-4 studies on macrophages help to characterize functional features of alveolar macrophages and their role in the early pathogenesis of pneumonia
10. Impact 10: OBJECTIVE 2 (Impact of Findings Continued): Minnesota: A clear understanding of the molecular basis of leukotoxin interaction with bovine leukocytes will facilitate development of new anti-shipping fever therapies, particularly those that are able to target the leukotoxin-receptor interaction and prevent the generation of inflammatory mediators
11. Impact 11: OBJECTIVE 2 (Impact of Findings Continued): Mississippi: DNA adenine methylase is a newly discovered virulence factor of Pasteurella multocida, and further characterization of this protein may lead to discovery of new virulence genes and a live attenuated vaccine
12. Impact 12: OBJECTIVE 2 (Impact of Findings Continued): Missouri: Characterization of MMP produced by the lung and inflammatory cells will allow us to determine their role in the pathology produced by bacterial infection. Depending upon their participation, synthetic MMP inhibitors may prove useful in pre-conditioning programs
13. Impact 13: OBJECTIVE 2 (Impact of Findings Continued): Nebraska: Development of alternatives to MLV vaccines against BHV 1, such as peptide vaccines adjuvanted with heat shock proteins such as gp96, should help to control this economically important disease. Research to elucidate the role of the LR transcript in pathogenesis should lead to development of vaccines or other strategies aimed at decreasing latency of BHV-1, which would help to limit spread of the virus in cattle populations
14. Impact 14: OBJECTIVE 2 (Impact of Findings Continued): Oklahoma: The identification, cloning, and production of subunit components of M. haemolytica and P. multocida offer opportunity for new bacterial vaccines to control BRD
15. Impact 15: OBJECTIVE 2 (Impact of Findings Continued): Wisconsin: Studies of the effect of LKT on bovine leukocytes should help clarify mechanisms to prevent cellular damage and the resultant impact on the immune response to M. haemolytica infection. Research to determine the mechanisms by which H. somnus induces thrombosis and vasculitis will provide a baseline for development of therapeutic strategies to mitigate the most severe effects of H. somnus infection
16. Impact 16: OBJECTIVE 3 (Impact of Findings): Alabama: Strategies to prevent entry of BVDV PI cattle into feedlots could impact morbidity and average daily gain of feedlot cattle
17. Impact 17: OBJECTIVE 3 (Impact of Findings Continued): California: Vaccination with a DNA vaccine expressing the BRSV NP protein shows promise for effective immunization against BRSV without disease enhancement
18. Impact 18: OBJECTIVE 3 (Impact of Findings Continued): Georgia: Mechanisms other than a strong T helper 1 cytokine response could be related to the protection afforded by IN vaccination; the response to IN vaccination warrants further study to determine the immunologic mechanisms associated with protection vs. disease enhancement
19. Impact 19: OBJECTIVE 3 (Impact of Findings Continued): Iowa: Innate immune responses constitute an early response to infections. Since M. bovis activates WC1+/gamma delta&#61472;T cells, it is presumed that these cells may play a role in early defenses against infection with this mycoplasma
20. Impact 20: OBJECTIVE 3 (Impact of Findings Continued): Kansas: Near-infrared spectroscopy is a potential diagnostic and prognostic tool that could be of value in field situations
21. Impact 21: OBJECTIVE 3 (Impact of Findings Continued): Louisiana: The findings indicate that novel antimicrobial proteins such as cecropin B may be useful in inhibiting M. haemolytica 1:A colonization. This work will add important facts to the database necessary to plan strategies for control of BRD
22. Impact 22: OBJECTIVE 3 (Impact of Findings Continued): Mississippi: Eliminating BVDV PI calves from the feedlot may reduce feedlot morbidity and increase performance
23. Impact 23: OBJECTIVE 3 (Impact of Findings Continued): NADC: A simple and effective means of vaccination could increase the usage of biologicals in at-risk transported cattle and reduce our reliance on antimicrobials. Effective non-injectable disease control methods could reduce industry problems with injection-site reactions. BVDV continues to cause problems with the health and performance of feedlot calves
24. Impact 24: OBJECTIVE 3 (Impact of Findings Continued): Oklahoma: Cattle receiving BVDV1a vaccines may not be protected against antigenically diverse strains such as BVDv1b. Vaccine recommendations for cattle prior to entering feedyard should stress BVDV vaccines to be used prior to shipping. Effective immunization against P. multocida should be investigated
25. Impact 25: OBJECTIVE 3 (Impact of Findings Continued): South Dakota: Vaccination with inactivated vaccines during the dry period may provide immunity comparable to modified live vaccines in some instances
26. Impact 26: OBJECTIVE 3 (Impact of Findings Continued): Texas: Control of oxidant activity could be a useful adjunct to therapy for BRD. Dual prophylaxis may be superior to vaccination alone or metaphylactic treatment alone to decrease morbidity and mortality due to BRD in the receiving period
27. Impact 27: OBJECTIVE 3 (Impact of Findings Continued): Wisconsin: Studies of the impact of barn design on calf pneumonia will help producers make design choices and other changes that could decrease the prevalence of calf respiratory disease

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Report Information

Participants

Participant list:
" Briggs, Robert (bbriggs@nadc.ars.usda.gov) - USDA, ARS, National Animal Disease Center;
" Chase, Chris (christopher_chase@sdstate.edu) - South Dakota State U;
" Chowdhury, Shafiqul (chowdh@vet.k-state.edu) - Kansas State U;
" Czuprynski, Chuck (czuprync@svm.vetmed.wisc.edu) - U of Wisconsin;
" Confer, Anthony (aconfer@okstate.edu) - Oklahoma State U;
" Gershwin, Laurel (ljgershwin@ucdavis.edu) - U of California, Davis;
" Grooms, Dan (groomsd@cvm.msu.edu) - MI); Michigan State U;
" Hurley, David (dhurley@vet.uga.edu) - U of Georgia;
" Lakritz, Jeff (lakritz.l@osu.edu)  Ohio State U;
" Maheswaran, Sam (mahes001@tc.umn.edu) - U of Minnesota;
" Srikumaran, Sri (ssrikumaran1@unl.edu)  U of Nebraska;
" Jones, Clint (cjones@unl.edu)  U of Nebraska;
" Woolums, Amelia (awoolums@vet.uga.edu) - U of Georgia;
" Asem, Eli (asem@purdue.edu)  Purdue U;

Brief Summary of Minutes

The meeting was opened with welcomes from Dr. Nelson Dean of College of Agriculture and Life Sciences, University of Nebraska-Lincoln and Dr. Rod Moxley, interim Head, Veterinary Biomedical Sciences. A brief history of the Arbor Day Foundation and the originations of Arbor Day followed.


BUSINESS MEETING: September 15, 2004


Updates from the Administrative Advisor: Dr Asem opened by congratulating Dr. Sri Srikumaran for his appointment at Washington State University and thanked him for organizing a nice meeting. He also thanked Drs. Amelia Woolum, David Hurley and Dan Grooms for writing the NC-107 Impact Statement requested by the NCRA office on behalf of the technical committee. Dr. Asem distributed copies of NCRA Newsletters to the group. Dr. Asem announced that the mid-term critical review of progress made by the NC-107 technical committee occurred in Winter, 2004. The results were positive. He reminded the group that the criteria used for the mid-term review were: Progress by station; Linkages between states and members; Funding out side the project; Information and technology transfer. Dr. Asem reminded the group that documentation of inter-station interactions and collaborations are very important for all multi-state technical committees including NC-107. Dr. Asem suggested that all future station reports should include detailed descriptions of inter-state interactions and collaborations as well as information about extramural funding.

FUTURE NC-107 FIVE-YEAR PROJECT
It was announced that the future project of NC-107 is due December, 2005; only three months after the 2005 annual meeting. It was suggested that the drafting of a new project should start very soon and communications should be held between members to assemble a full draft that would be discussed at the next annual meeting. Also, it was suggested that following next annual meeting the project should be reviewed by non-members prior to its submission A project-writing committee was elected. The members are Dr. Christopher Chase, Dr. Amelia Woolums, Dr. Dan Grooms, Dr. Dave Hurley (coordinator).


Discussion on loss of support for regional projects:
" Seems to be lost between program office and workers in field.
" Experimental Director and Dean split pool of total
" Often used, on state level for salary support and infrastructure, but not often direct project support.
" Looking to move toward an opportunity to seek funding to promote multi-investigator projects as part of NC project.
" Power in hands of experimental station.
" Projects to other competitive source, like HAS, are becoming more common
" This is a good group, but we must move forward with the times.
" Need to view as opportunity with a great group potential.
" Redirect the approach, look at group funding opportunities outside of USDA to focus group with funded collaboration.
" May need a more narrow focus that has deep common threads.
" Build project to enhance chances of multicenter project.
" Currently, we are looking at individual funding to move a broad scope.


New Station Representatives:
" Texas Dr. Guy Lonegran
" Ohio none (Dr. Jeff Lakritz guest)
" Nebraska Dr. Clint Jones


Officers Elected for 2005:
" Chair: Dr. Dave Hurley
" Secretary: Dr. Shafiqul Chowderi


Future Meeting Locations:
" California 2005
" Georgia 2006
" Minnesota 2007


Assigned responsibilities:
Dr. Grooms will prepare this years annual report and forward to Dr. Asem for submission. Dr. Hurley (Chair for 2004-2005) will communicate with Dr. Gershwin (in charge of local arrangements for the 2005 meeting) and Dr. Asem in coming months to distribute information regarding the next meeting. Dr. Hurley will distribute minutes and updated address list for group. Dr. Chowdhury (KS) will serve as the Secretary for 2005 and Chair for 2006.


Next meeting information:
Sept (day TBA), 2005, at California. Dr. Gershwin will coordinate local arrangements.


Business Meeting closed on September 15, 2004 at 11:30am



Station Reports were given by the following:

California Dr. Laurel Gershwin
Georgia Dr. David Hurley
Kansas Dr. Shafiqul Chowdhury
Michigan Dan Grooms
Minnesota Dr. Sam Mahashwan
Nebraska Dr. Clint Jones and Dr. Sri Srikumaran
Oklahoma Dr. Anthony W. Confer
South Dakota Dr. Chris Chase
Wisconsin Dr. Chuck Czuprynski
USDA-NADC Dr. Bob Briggs

Accomplishments

<B>OBJECTIVE 1: </B>Identify emerging and re-emerging agents and develop diagnostic methods for bovine respiratory disease (BRD). <br /> <br /> South Dakota:<br /> Immunoperoxidase BVDV outgrowth test for the detection of BVDV PI animals was used on 7409 animals and there were 17 positives. Ear notch BVDV tests were conducted on 21,048 samples and there were 150 positives. PCR tests were done for BVDV and 316 tests (1547 samples) were tested and 39 positives were detected. <br /> <br /> Georgia:<br /> In the past year a survey was initiated to characterize the prevalence of Mycoplasma bovis at 10 Georgia backgrounding/stocker operations. <br /> <br /> Michigan:<br /> Mycoplasma bovis (M. bovis) has been identified as an emerging pathogen in feedlot calves and is believed to be responsible for an increasing incidence of nonresponsive chronic pneumonia, polyarthritis and mortality. In a survey of causes of mortality in Michigan fed cattle, M. bovis was identified as the major bacteria associated with pneumonia related mortality.<br /> <br /> A conductometric biosensor has been developed and was shown to accurately and rapidly detect BVDV in cell culture.<br /> <br /> Mississippi:<br /> By comparing transcriptional regulator gene sequences from the P. multocida genome with other DNA sequences at GenBank, two genes (Pm0762 and Pm1231) were identified that are uniquely present in this species. <br /> <br /> Oklahoma:<br /> A total of 390 (46.3%) Mannheimia haemolytica, 292 (34.7%) Pasteurella multocida, and 160 (19.0%) Haemophilus somnus were isolated at the Oklahoma Disease Diagnostic Laboratory from lungs from 6-18 month old beef cattle with pneumonia. The frequency of isolation of M. haemolytica decreased from 62.5% in 1994 to between 30.6% and 50.4% in 1998  2002. The frequency of isolation of P. multocida increased from 20.0% in 1994 to between 28.6% and 47.4% in 1998  2002. H. somnus isolations were <19% except in 1998 (40.8%) and 1999 (23%). <br /> <br /> An observation study of 30 dairy heifers from birth to breeding age indicated transmission of potential respiratory pathogens by serology despite commonly accepted health management programs including vaccination. <br /> <br /> A genetically distinct BVDV2a NCP strain was isolated from persistently infected (PI) calves born to vaccinated heifers receiving BVDV1a and BVDV2a CP strains. <br /> <br /> Comparison of infectious agent isolations and lesions in lungs of cattle dying in a feedlot were made to clinical data and treatment information including: fatal disease onset (FDO); treatment death interval; day of death in feedlot; and number of treatments. Diverse strains of BVDV were isolated from feedlot cattle including BVDV1b, BVDV1a, BVDV2a, and BVDV2b. Mycoplasma spp were isolated from these feedlot pneumonias with 72% of the Mycoplasma spp being M. bovis. Ear notches from 1325 cattle dying in feedlots (five) were tested by BVDV IHC with 4.1% positive. <br /> <br /> Ear notches stored in 10% neutral buffered formalin remained BVDV IHC positive after extended storage: up to one year (one calf positive after 4 years). <br /> <br /> <br /> <B>OBJECTIVE 2:</B> Characterize mechanisms and intervention targets in pathogenesis of BRD at the molecular, cellular, and host level.<br /> <br /> California: <br /> Using the calf lung lymph cannulation model over the past three years we have addressed the hypothesis that infection with BRSV facilitates development of IgE antibodies to inhaled allergen when the allergen is presented during the acute phase of the viral infection.<br /> <br /> Examined the effect of concurrent vaccination with BRSV killed vaccine and H. somnus bacterin on development of the Th2 profile, IgE, and clinical severity of disease after experimental infection.<br /> <br /> Extended our previous observations that BRSV infection can enhance allergic sensitization to inhaled M. faeni to examine the effect of aerosol exposure to the fungal allergen Alternaria alternata (prior to and during initial BRSV infection) on the immune response and clinical outcome of a secondary BRSV infection. <br /> <br /> South Dakota:<br /> We have developed a real time PCR test for the detection of Toll-like receptors 2 and 4 to be used in assessing the interaction of BVDV with macrophages.<br /> <br /> We investigated the effect of wild-type (WT) or mutant strains (Vk36 [gI-], Vk25 [gE-], gED3.1 [gE-], & V20 [gI- and gE-]) of BHV-1 on the integrity of cytoskeleton components, actin filaments (AF), microtubules (MT) and intermediate filaments (IF) during the course of viral infection.<br /> <br /> Georgia: <br /> The progression of immune activities following vaccination with modified live virus (MLV) or killed bovine viral diarrhea (BVD) virus was evaluated. <br /> <br /> The effect of pH on the function of blood leukocytes was evaluated by assessing the effects of extracellular pH on phagocytosis of bacteria and production of reactive oxygen species (ROS). <br /> <br /> We examined the comparative activity of Salmonella, E. coli and Rhizobial lipopolysaccharide in induction of nitric oxide (NO) and radical oxygen species (ROS). <br /> <br /> Iowa:<br /> A lymphocyte-suppressive activity of Mycoplasma bovis was found to reside in a peptide cleaved off a surface-exposed membrane protein of the organism. The native, or recombinant form of this peptide had suppressive activity.<br /> <br /> Cultured bovine pulmonary microvascular endothelial cells were found to preferentially respond with mRNA transcripts signaling mononuclear cell transmigration (VCAM-1, RANTES) after infection with Mycoplasma bovis. Abscessing and non-abscessing strains of M. bovis induced the same types of transcripts. In contrast, aortic endothelial cells were found to be less reactive.<br /> <br /> Kansas:<br /> Using an intranasal infection model in rabbits, both BHV-1 and BHV-5 can be differentiated based on their neuropathogenesis. In the rabbit model, both viruses infect the olfactory receptor neurons (ORN), however only BHV-5 can invade the secondorder neurons in the olfactory bulb. <br /> <br /> Mississippi:<br /> Two dimensional capillary liquid chromatography followed by electrospray-ionization ion-trap tandem mass spectrometry (2-D µLC ESI MS/MS) was used to compare outer membrane protein fractions from M. haemolytica and H. somnus grown under sub-MIC antibiotic and no antibiotic conditions.<br /> <br /> We used noncytopathic (ncp) and cytopathic (cp) bovine viral diarrhea viruses (BVDV) to determine how the two biotypes affect mannose receptor (MR)-mediated endocytosis and fluid phase uptake in bovine monocytes.<br /> <br /> NADC:<br /> Respiratory dendritic cells were isolated using magnetic-activated cell sorting. These cells are being used for studies on BRSV.<br /> <br /> Serial analysis of gene expression (SAGE) was used to identify differential gene expression in cultured epithelial and lymphatic cells following infection with BVDV. Changes were found that indicated increased protein translational potential, increased nascent peptide transport and enhanced intracellular membrane targeting and transport.<br /> <br /> Nebraska:<br /> A novel BHV-1 gene that is expressed in trigeminal ganglia of latently infected calves (ORF-E) was discovered. <br /> <br /> The BHV-1 LR gene encodes multiple functions that together regulate latency. The dominant function is performed by a protein encoded by ORF-2 that is absolutely required for the latency-reactivation cycle in cattle.<br /> <br /> Using a vaccinia virus T7-promoter expression system, expression of the single and combination N-glycosylation deletion F proteins of BRSV was characterized in COS-7 cells. <br /> <br /> Subtle differences in primary and secondary structures of the 5UTR of BVDV was shown to influence translational efficiencies.<br /> <br /> BRSV or BVDV infection reduced intracellular GSH levels in PBMCs and NK cells and suppressed their functions.<br /> <br /> Minnesota:<br /> Expression of the reputed M. haemolytica leukotoxin receptor, bovine LFA-1, in the human erythroleukemic K562 cell line was successfully accomplished. The expressed product was also found to be functionally active.<br /> <br /> M. haemolytica leukotoxin induced oncosis was shown to proceed thru a LFA-1 and caspase-1 dependent pathway as well as an independent pathway.<br /> <br /> Oklahoma:<br /> An epitope of PI pE, a particular OMP from serotype 1 M. haemolytica was identified as responsible for immunity in calves resistant to challenge. <br /> <br /> <br /> <B>OBJECTIVE 3:</B> Develop intervention strategies for critical control points to reduce the impact of BRD.<br /> <br /> California:<br /> Following the success of a pilot experiment last year, we have been further developing the DNA vaccine (producing sufficient plasmid for inoculation of calves in a larger scale experiment) using the N protein and will be performing another experiment during this next year. <br /> <br /> South Dakota:<br /> A study was done using a commercial modified live virus vaccine containing bovine herpesvirus-1 (BHV-1), causative agent of IBR, given intramuscularly to calves 48, 72, and 96 hours (hr) prior to an intranasal challenge with BHV-1. A study was done using a commercial modified live virus vaccine containing bovine herpesvirus-1 (BHV-1), causative agent of IBR, given intramuscularly to calves 48, 72, and 96 hours (hr) prior to an intranasal challenge with BHV-1. <br /> <br /> Kansas:<br /> Near infrared spectroscopy (NIRS) was evaluated in a feedlot study as a means of noninvasively determining oxygen saturation StO2 of hemoglobin to identify animals as having undifferentiated bovine respiratory disease (UBRD). <br /> <br /> Louisiana:<br /> Cecropin B is very effective in inhibiting M. haemolytica 1:A. Transfecting the upper respiratory tract of cattle with a gene coding for cecropin B does not result in a change in the indigenous and transient nasal flora. Results indicate that transfecting the upper respiratory tract with 100 ¼g of DNA per nostril does inhibit colonization of a virulent strain of M. haemolytica 1:A. <br /> <br /> NADC:<br /> The usefulness of an oral vaccine against M. haemolytica/P. multocida was evaluated in a field stuffy. The vaccine was shown to be effective in reducing the colonization and shedding of M. haemolytica A1 but not heterologous serotypes of the same bacteria.<br /> <br /> Oklahoma:<br /> Prior vaccination with MLV BVDV vaccine protected susceptible calves against viremia after exposure to BVDV PI calves. The contribution of intracellular calcium stores to M. haemolytica leukotoxin induced increase in cystolic calcium concentration was confirmed by inhibitors of calcium across membranes.<br /> <br /> <br /> <B>INTER-STATION COLLABORATIVE EFFORTS</B><br /> <br /> SD, NE, OK and AL collaborated on an issue of Veterinary Clinics of North America focused on bovine viral diarrhea virus<br /> <br /> SD and MI collaborated with CA on a book titled 5-Minute Veterinarian<br /> <br /> MI worked with SD, KS, OK, AL, OH and NADC in identifying cattle persistently infected with BVDV for natural fetal challenge study.<br /> <br /> SD, GA, CA, and NE collaborated on BRSV challenge models<br /> <br /> SD, AL, MI, and NADC shared various BVDV strains and collaborated on developing new challenge models.<br /> <br /> SD and GA collaborated on bovine immunology studies.<br /> <br /> SD shared BHV-1 strains with KS, U of Pennsylvania and Princeton.<br /> <br /> NE, GA and CA collaborated on a vaccinology course for veterinarians and veterinary students. <br /> <br /> OH worked with SD, KSU, CA, IA, WCVS and Pfizer in developing and teaching a graduate level course in vaccinology. <br /> <br /> GA collaborated with University of Montreal and NIH on new vaccine vehicles and delivery systems.<br /> <br /> GA collaborated with Merial in measuring vaccine efficacy across a multi assay platform.<br /> <br /> KS and NE shared reagents related to BHV-1 and BHV-5 research.<br /> <br /> CA shared BRSV isolates with SD and U of Tennessee.<br /> <br /> NADC and OK in constructing and evaluating new mutant P. multocida vaccine.<br /> <br /> NADC, OK and New Mexico State on evaluating mucosal immunity to oral M. haem/P. multi vaccine<br /> <br /> NADC and MN collaborated on generating leukotoxin knock out mutants of M. haemolytica.<br /> <br /> NADC, NE, OK, WI and MN share monoclonal antibodies directed against M. haemolytica leukotoxin.<br /> <br /> OK and NADC collaborated on sequencing of multiple BVDV isolates.<br /> <br /> <b>IMPACTS OF FINDINGS</b><P><br /> OBJECTIVE 1: Data regarding the prevalence of Mycoplasma bovis in Georgia backgrounded/stocker cattle will provide producers, veterinarians, and researchers with previously unavailable information to assist their decision making regarding practices related to control of disease due to M. bovis. A rapid detection of BVDV in cell culture media using a biosensor has been demonstrated. Further development may make this a useful tool for the rapid and economical identification of BVDV PI cattle. Bronchopneumonia continues to be the major cause of feedlot morbidity. However the major pathogen associated with bronchopneumonia morbidity in Michigan appears to be Mycoplasma bovis. BVDV is often found in conjunction with M. bovis as well as other respiratory pathogens. PCR targeting Pm0762 and Pm1231 from Pasteurella multocida provides a useful means of rapidly and precisely identifying this species and differentiating it from other species.<br /> <br /> OBJECTIVE 2: Data from the study of the agreement between various assays of cell mediated immunity in calves vaccinated against BVD should improve the ability of researchers to make choices regarding which assays of cell mediated immunity are appropriate when they design research projects to characterize vaccines. Data indicating that changes in pH affect the function of leukocytes should provide impetus to manage cattle in ways that minimize the development of diseases (such as acidosis or diarrhea) that have a major impact on pH. Studies on the lympho-suppressive activity of M. bovis and the interaction of the mycoplasma with endothelial cells provide basic knowledge for the description of virulence factors of the mycoplasma, and for understanding how lung lesions develop during respiratory infection and its systemic components. Toll like receptor 2 and 4 real time PCR assays was developed for molecular pathogenesis studies with BVDV and macrophages were conducted. Studies have helped define the comparative pathogenesis of neurovirulent (BHV-5) and non-neurovirulent (BHV-1) bovine herpesviruses and the role of Us9 in anterograde neuronal transport. A clear understanding of the molecular interactions of the M. haemolytica leukotoxin at the cellular level could lead to new novel preventions and therapies for BRD.<br /> <br /> OBJECTIVE 3: Antimicrobial peptides such as cecropin B are useful in inhibiting M. haemolytica 1:A colonization. Sub-MICs of antibiotics effect protein expression in M. haemolytica, H. somnus, and P. multocida, including some proteins that could be important for virulence. These findings may elucidate the mechanism behind the beneficial effects of prophylactic antibiotic use in cattle. <br />

Publications

FUNDING SUPPORT<br /> <br /> <br /> Prevalence of mycoplasma infection in Georgia cattle. Woolums A, Sanchez S, Pence M, Cole D, Ensley D. Support from the University of Georgia College of Veterinary Medicine Food Animal Health Management Program. October 2002-June 2004. $10,000.<br /> <br /> <br /> Preliminary prevalence study of Mycoplasma bovis and Mycoplasma sp. in selected Dairy and beef herds in Georgia. Giusto N, Woolums AR, Sanchez. Project for Georgia Veterinary Scholars Program participant Nicole Giusto, sophomore veterinary student.May-August 2003. Funded by the Merck Foundation andMerial Ltd. $5000.<br /> <br /> <br /> Multidisciplinary evaluation of fatal feedlot ARDS. Woolums AR, principle investigator. Hawkins L, Brown C, Hungerford L, Loneragan G, Mason G, co-investigators. USDA National Research Initiative Competitive Grants Program. September 2000-August 2004. $240,000<br /> <br /> <br /> Comparison of the capacity of in vitro tools to assess the immune response of cattle to inactivated and modified-live vaccines and their relationship to protection from infection and acute disease. Hurely, D.J, Woolums, A.R, Reber, A.J. and Okinaga, T.March. GRA- Merial LTD. 2003-December 2004. $181,000<br /> <br /> <br /> The role of infectious agents in chronic respiratory diseases: (UGA)Hurley, D.J. (coordinator), Woolums, A., Moore, J.N., Krunkosky, T.M., Krause, D.Terry Respriatory Disease Fund. January 2003  December 2004. $76,000.<br /> <br /> <br /> Interaction of H. somnus and purinoceptors, in apoptosis of endothelial cells. Czuprynski, Charles J. USDA NRI CGP. 07/01/00-06/30/04. $180,000 <br /> <br /> <br /> Cytokine-mediated enhancement of the susceptibility of bovine leukocytes to Pasteurella haemolytica leukotoxin. Czuprynski, Charles. WI Ag. Experiment Station 10/01/01-09/30/04. $87,000.<br /> <br /> <br /> Evolving Pathogens, targeted sequences and strategies for control of bovine respiratory diseases. Czuprynski, Charles. WI Ag. Experiment Station 10/01/01-09/30/04. $66,000<br /> <br /> <br /> Integrin-dependent signaling and exacerbation of the leukocyte response to Mannheimia haemolytica leukotoxin by virus infection and cytokines. Czuprynski, Charles. USDA NRICGP 07/01/04-06/30/07. $370,000.<br /> <br /> <br /> Role of caspase-9 activation and mitochondria in Mannheimia haemolytica leukotoxin mediated apoptosis in bovine leukocytes. Czuprynski, Charles. WI Ag. Experiment Station 10/01/04-09/30/07. $88,000 <br /> <br /> <br /> Microvascular endothelial cell response to Haemophilus. Czuprynski, Charles. NIH K08. 12/01/03  11/30/07. $286,000.<br /> <br /> <br /> Contrast in lung immune responses after chronic Mycoplasma bovis infection or vaccine-induced susceptibility. Ricardo F. Rosenbusch. USDA Formula Funds Oct 03Sep 04. $20,000<br /> <br /> <br /> Immune-mediated lung damage in Mycoplasma bovis infection. Ricardo F. Rosenbusch. Healthy Livestock for Iowa. Jul 03  Jun 04. $19,996.<br /> <br /> <br /> Testing a newly discovered peptide as a unique immunosuppressive agent. Ricardo F. Rosenbusch. Carver Trust. 16 Apr 03-31 Jul 04. $23,804.<br /> <br /> <br /> Extracts of Mycoplasma bovis as antigens for vaccines. Ricardo F. Rosenbusch. Boehringer Ingelheim Vetmedica, Inc. Oct 00- Jun 04. $189,794. <br /> <br /> <br /> Role ofgE and gI in BHV-1 and BHV-5 differential neuropathognesis. USDA NRI. Shafiqul I. Chowdhury 2001-2003. $285,000.<br /> <br /> <br /> LPS induced lung inflammation: a model to characterize the role of matrix metalloproteinases in bovine respiratory disease. Lakritz J, Mattoon J, Abrahamsen E, Marsh AE, Weisbrode S. USDA CSREES 2004-2007 $350,000. <br /> <br /> <br /> The role of dendritic cells in the bovine viral diarrhea virus antigen presentation. Pinchuk, LM. USDA/NRICGP Seed Grant. 2002-2003, $74,778.<br /> <br /> <br /> Mannheimia haemolytica outer membrane protein PlpE: Characterization of epitopes stimulating homologous and heterologous serotype protection. Anthony Confer. USDA CSREES,National Research Initiative Competitive Grant. 2002-2005 (Grant # 2002-02232). $290,000<br /> <br /> <br /> Chimeric Vaccine for Mannheimia haemolytica Infection in Cattle. Oklahoma Applied Research Program. Oklahoma Center for the Advancement of Science and Technology (OCAST). 2003-2005. $259,395.<br /> <br /> <br /> Evaluation of Mannheimia haemolytica and Pasteurella multocida vaccines. Anthony Confer. Fort Dodge Animal Health, Inc. 2003-2005. $95,779.<br /> <br /> <br /> The Production of mAb Using cDNA from E2 and Npro-C-Erns Region of Bovine Viral Diarrhea Virus (BVDV) <br /> Vaccine 1b Isolate. Chris Chase. Novaritis Animal Health. 2003-2005. $23,9800.<br /> <br /> <br /> Center for Infectious Disease and Vaccinology. State of South Dakota. Chris Chase. 6-04 to 5-09. $4,000,000.<br /> <br /> <br /> Importance of Mycoplasma bovis in Michigan Feedlots. Dan Grooms. Michigan <br /> Animal Industry Coalition. 2003-2004. $32,740, <br /> <br /> <br /> Biosensor development for agrisecurity. Dan Grooms. Michigan Animal Industry Coalition. 2003-2004. $29,672.<br /> <br /> <br /> <br /> <br /> <br /> PUBLICATIONS<br /> <br /> PEER-REVIEWED MANUSCRIPTS:<br /> <br /> Kalina WV, Woolums AR, Berghaus RD, Gershwin LJ. Formalin-inactivated bovine RSV vaccine enhances a Th2 mediated immune response in infected cattle. Vaccine 22 (11-12):1465-74. 2004<br /> <br /> <br /> Donovan DC, AR Hippen, DJ Hurley and CCL Chase. 2003. The role of acidogenic diets and serum antibody response against bovine respiratory viruses in Holstein steers. J. Anim. Sci. 81:3088-3094.<br /> <br /> <br /> Fogarty Fairbanks, K, J Campbell and CCL Chase. 2004. Rapid onset of protection against infectious bovine rhinotracheitis with a modified-live virus multivalent vaccine. Vet.Therapeutics 5:17-25.<br /> <br /> <br /> Chase CCL, G Elmowalid and AAA Yousif. 2004. The immune response to bovine viral diarrhea virus: a constantly changing picture. Vet Clin Food Anim 20:95114. <br /> <br /> <br /> Chase CCL, G Elmowalid, LJ Braun and JF Ridpath. New paradigms for bovine viral diarrhea virus: understanding how BVDV interacts with the immune system. 36th annual conference of American Association of Bovine Practitioners, Columbus, OH, September 18-20, 2003, p. 189.<br /> <br /> <br /> Hassan EAD, LJ Braun and CCL Chase. Interaction of bovine herpesvirus-1 glycoproteins with cellular cytoskeletal elements in bovine herpesvirus-1 infected cells. Abstract 130P. 84th annual meeting of Conference of Research Workers in Animal Disease, Chicago, IL, November 9-11, 2003. <br /> <br /> <br /> Hassan EAD, LJ Braun and CCL Chase. Effect of protein kinase inhibitors on the replication of bovine herpesvirus-1 (BHV-1). Abstract 174. 84th annual meeting of Conference of Research Workers in Animal Disease, Chicago, IL, November 9-11, 2003.<br /> <br /> <br /> Miao C, Woolums AR, Zarlenga D, Brown C, Brown Jr JC, Williams S, Scott M. Effects of a single intranasal dose of modified-live bovine respiratory syncytial virus vaccine on cytokine messenger RNA expression following viral challenge in calves. Am J Vet Res. June 2004. <br /> <br /> <br /> Woolums AR, Brown C, Brown Jr JC, Cole D, Scott M, Williams S, Miao C. Effects of a single intranasal dose of modified-live bovine respiratory syncytial virus vaccine on resistance to subsequent viral challenge in calves. Am J Vet Res. 2004; 65:363-372.<br /> <br /> <br /> Vanden Bush T. J., and R. F. Rosenbusch. 2004. Characterization of a lympho-inhibitory peptide produced by Mycoplasma bovis. Bioch. Biophys. Res. Comm. 315: 336-341.<br /> <br /> <br /> Al-Mubarak, A, Zhou, Y., and Chowdhury, S.I . (2004). A glycine rich region in the ecto domain of BHV-5 gE is important for BHV-5 neuropathogenesis. J. Virol. 78, 4806-4816.<br /> <br /> <br /> Boudreaux, CM and Corstvet, RE. A novel strategy of controlling shipping fever. The Louisiana cattleman, Official publication of the Louisiana Cattlemens Association, November 2003, 36(11):10-11.<br /> <br /> <br /> Bolin SR. Grooms DL. Origination and Consequences of Bovine Viral Diarrhea Virus Diarrhea Diversity. Vet Clin N Amer: Food An. 2004;20(1):51<br /> <br /> <br /> Liu, D., M. L. Lawrence, and F. W. Austin. 2004. Specific PCR identification of<br /> Pasteurella multocida based on putative transcriptional regulator genes. J.<br /> Microbiol. Methods 58(2):263-267.<br /> <br /> <br /> Jones, C. Analysis of HSV-1 and BHV-1 1 latency. 2003. Clinical Microbiology Reviews. 16:79-95<br /> <br /> <br /> Lovato, L., M. Inman, G. Henderson, A. Doster., and C. Jones, C. 2003. Infection of cattle with a bovine herpesvirus 1 (BHV-1) strain that contains a mutation in the latency related gene leads to increased apoptosis in trigeminal ganglia during the transition from acute infection to latency. J of Virology, 77:4848-4857.<br /> <br /> <br /> Geiser, V. and C. Jones. 2003. Stimulation of bovine herpesvirus 1 productive infection by the adenovirus E1A gene and the cellular transcription factor E2F4. J. of General Virology, 84:929-938.<br /> <br /> <br /> Mott, K., N. Osorio, L. Jin, D. Brick, J. Naito, J. Cooper, G. Henderson, M. Inman, C. Jones, S. L. Wechsler, and G.-C. Perng. 2003. The BHV-1 LR genes ability to restore the high reactivation phenotype to an HSV-1 LAT null mutant appears to be due to its anti-apoptosis function. J. of General Virology, 84:2975-2985.<br /> <br /> <br /> Devireddy, L., Y. Zhang, and C. Jones. 2003. Cloning and initial characterization of an alternatively spliced transcript encoded by the bovine herpes virus 1 latency related (LR) gene. J. of Neurovirology, 9: 612-622.<br /> <br /> <br /> Henderson, G., G.-C. Perng, A. B. Nesburn, S. L. Wechsler, and C. Jones. 2004. The latency related (LR) gene encoded by bovine herpesvirus 1 (BHV-1) can suppress caspase 3 and caspase 9 cleavage during productive infection. J. of Neurovirology, 10:64-70.<br /> <br /> <br /> Jiang, Y., M. Inman, Y. Zhang, N. A. Posadas , and C. Jones. 2004. A mutation in the latency related gene of bovine herpesvirus 1 (BHV-1) inhibits expression of proteins encoded by ORF2 and Reading Frame C during productive infection. J. of Virology 78:3184-3189. <br /> <br /> <br /> Inman, M., J. Zhou, H. Webb, and C. Jones. 2004. Identification of a novel transcript containing a small open reading frame that is expressed during latency, and is antisense to the latency related gene of bovine herpes virus 1 (BHV-1). J. of Virology 5438-5447.<br /> <br /> <br /> Fulton, R.W., Briggs, R.E., Payton, M.E., Confer, A.W., Saliki, J.T., Ridpath, J.F., Burge, L.J., Duff, G.C.: Maternally Derived Humoral Immunity to Bovine Viral Diarrhea Virus (BVDV)1a, BVDV1b, BVDV2, Bovine-Herpesvirus-1, Parainfluenza-3 Virus, Bovine Respiratory Syncytial Virus, Mannheimia haemolytica and Pasteurella multocida in Beef Calves, Antibody Decline by Half-life studies and Effect on Response to Vaccination. Vaccine, 22:644-650, 2004.<br /> <br /> <br /> Berry, B.A., Krehbiel, C.R., Gill, D.R., Confer, A.W., Smith, R.A., Montelongo, M.: Effects of Dietary Energy and Starch Concentrations for Newly Received Feedlot Calves: I. Growth Performance and Health. J Anim Sci. 82:837-844, 2004.<br /> <br /> <br /> Berry, B.A., Confer, A.W., Krehbiel, C.R., Gill, D.R., Smith, R.A., Montelongo, M.: Effects of Dietary Energy and Starch Concentrations for Newly Received Feedlot Calves: II. Acute-phase protein response. J Anim Sci. 82:845-850, 2004.<br /> <br /> <br /> Dabo, S.M., Confer, A.W., Quijano-Blas, R.A.: Molecular and Immunological Characterization of Pasteurella multocida A:3 OmpA: Evidence of its Role in P. multocida Interaction with Extracellular Matrix Molecules. Microb Pathog. 35:147-157, 2003.<br /> <br /> <br /> Cudd, L.A., Clarke, C.R., Clinkenbeard, K.D.: Mannheimia haemolytica Leukotoxin-Induced Increase in Leukotriene B4 Production by Bovine Neutrophils is Mediated by Sustained and Excessive Increase in Intracellular Calcium Concentration. FEMS Micro. Let. 224:85-90, 2003.<br /> <br /> <br /> Cudd, L.A., Clarke, C.R., Clinkenbeard, K.D.: Contribution of Intracellular Calcium Stores to an Increase in Cytosolic Calcium Concentration Induced by Mannheimia haemolytica Leukotoxin. FEMS Micro. Let. 225:23-27, 2003.<br /> <br /> <br /> Malazdrewich CP, Thumbikat MS, Abrahamsen MS, Maheswaran SK. Pharmacological inhibition of Mannheimia haemolytica lipopolysaccharide and leukotocin-induced inflammatory cytokine expression in bovine alveolar macrophages. Microbial Pathogenesis. 2004;36:159-169.<br /> <br /> <br /> Malazdrewich CP, Thumbikat MS, Maheswaran SK. Protective effects of dexamathasone in experimental bovine pneumonic pasteurellosis. Microbial Pathogenesis. 2004;36:227-237.<br /> <br /> <br /> <br /> ABSTRACTS:<br /> <br /> L.J. Gershwin, L.B. Corbeil, L.J. Berghaus, K.F. Arnold, M.L. Anderson. IgE and Cytokine Profiles in Calves Concurrently Infected with BRSV and Histophilus somni. Presented at 7th International Veterinary Immunology Symposium, Quebec City, July 2004.<br /> <br /> <br /> Chase CCL, G Elmowalid, LJ Braun and JF Ridpath. New paradigms for bovine viral diarrhea virus: understanding how BVDV interacts with the immune system. 36th annual conference of American Association of Bovine Practitioners, Columbus, OH, September 18-20, 2003, p. 189.<br /> <br /> <br /> Hassan EAD, LJ Braun and CCL Chase. Interaction of bovine herpesvirus-1 glycoproteins with cellular cytoskeletal elements in bovine herpesvirus-1 infected cells. Abstract 130P. 84th annual meeting of Conference of Research Workers in Animal Disease, Chicago, IL, November 9-11, 2003. <br /> <br /> <br /> Hassan EAD, LJ Braun and CCL Chase. Effect of protein kinase inhibitors on the replication of bovine herpesvirus-1 (BHV-1). Abstract 174. 84th annual meeting of Conference of Research Workers in Animal Disease, Chicago, IL, November 9-11, 2003.<br /> <br /> <br /> Donovan DC, Reber AJ, Parks RJ, Collier C, Ely LO, and Hurley DJ. Extracellular pH alters the innate immune response by enhancing phagocytosis and decreases reactive oxygen species production. American Dairy Science Annual Meeting. St. Louis, MO. 2004; J Dairy Sci 87:179 (Suppl. 1).<br /> <br /> <br /> Donovan DC, Collier C, Reber AJ, Parks RJ, and Hurley DJ. Extracellular pH alters immunity by decreasing the production of reactive oxygen and nitrogen species, but enhancing phagocytosis in bovine neutrophils and monocytes. International Conference of Production Diseases in Farm Animals. Michigan State University. July 18-22, 2004.<br /> Abstract: A-14. <br /> <br /> <br /> Donovan DC, Reber AJ, Parks RJ, and Hurley DJ. Acidic extracellular pH enhances phagocytosis and decreases reactive oxygen species production in polymorphonuclear neutrophils and monocytes. 2004; 7th International Veterinary Immunology Symposium. WK 13.6.10 p 415. Quebec City, Qc. July 25-29, 2004. <br /> <br /> <br /> Reber, A.J., T. Okinaga, M. Tanner, A. Woolums, T. Leard, F. Milward, D.J. Hurley Evaluation of multiple immune parameters during development of immunity after vaccination with MLV or killed BVD. 7th International Veterinary Immunology Symposium. Program and Book of Abstracts, p. 150 (WK.1.6.7). Quebec City, Canada. July 25 - 30, 2004<br /> <br /> <br /> Hurley, D.J., Pence, M., Lee, Y., Reber, A.J. and Parks, R.J. 2003. Characterization of an immunological defect observed in a herd of Hereford cattle. Proceedings of the Conference of Research Workers in Animal Diseases. 84:102 <br /> <br /> <br /> Reber, AJ, Okinaga, T, Tanner, M, Woolums, A, and Hurley, DJ. .2003. Comparison of cytokine production assays after stimulation of bovine mononuclear cells with Staphylococcal enterotoxin B or vaccine recall antigen. Proceedings of the Conference of Research Workers in Animal Diseases. 84:73P<br /> <br /> <br /> Woolums AR, Mason G, Brown C, Williams S, Gould J, Fox J, Sturgeon S, Sanchez S, Bartlett P, Chitwood S. Microbiologic and histopathologic findings in cases of acute interstitial pneumonia (AIP) in feedyard cattle. Proceedings of the Conference for Research Workers in Animal Disease (CRWAD), Chicago IL, November 2003.<br /> <br /> <br /> Harden, TT, Paulsen, DB, Godeny, EK, Olcott, BM, Smith, SL, Triche, PC, and OReilly, KL. Respiratory bovine coronavirus-induced pneumonia in newborn calves: a pilot study. South Central Branch of the American Society for Microbiology, New Orleans, LA, October 24-25, 2003.<br /> <br /> <br /> OReilly, KL, Godeny, GK, Kousoulas, KG, Olcott, BM, Paulsen, DB, Harden, TT, Smith, S, and Triche, PC. Intrabronchial infection of newborn calves with respiratory bovine coronavirus. Animal Disease Research Workers of Southern States, Biloxi, MS, February 2004.<br /> <br /> <br /> Johnson, TK, Triche, PC, and OReilly, KL. Immune response of newborn calves to intrabronchial infection with bovine coronavirus. Meeting of the Louisiana Biomedical Research Network, Baton Rouge, LA, July 28, 2004.<br /> <br /> <br /> Nanduri, B., M. L. Lawrence, and S. C. Burgess. 2004. Determination of sub-MIC effects of antibiotics on Pasteurella multocida protein expression using cleavable isotope coded affinity tag reagents. 104th General Meeting of the American Society for Microbiology, New Orleans, Louisiana.<br /> <br /> <br /> <br /> DISSERTATIONS:<br /> <br /> Kalina, WV. The influence of Alternaria alternate Aerosol on the Development of Immune Responses in Calves During a Primary and Secondary Bovine Respiratory Syncytial Virus Infection. University of California, Davis, 2004.<br /> <br /> <br /> Hassan, Ehab. Investigation of the role of viral glycoproteins gE AND gI in bovine herpesvirus type 1 (BHV-1) pathogenesis: study of cytoskeleton and phosphorylation. PhD Dissertation, South Dakota State University, 2004.<br /> <br /> <br /> Fogarty-Fairbanks, Kristine. New clinical applications for three USDA licensed vaccines in the prevention of infectious bovine rhinotracheitis or bovine viral diarrhea virus. Master of Science Thesis, South Dakota State University, 2004.<br /> <br /> <br /> Anthony Vandenbush. 2003. Interactions between Mycoplasma bovis and bovine lymphocytes: characterization of a lympho-inhibitory peptide produced by Mycoplasma bovis. PhD Thesis, Iowa State University.<br />

Impact Statements

1. REFER TO ACCOMPLISHMENTS SECTION

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Report Information

Participants

Woolums, Amelia (awoolums@vet.uga.edu)- U of Georgia;
Hurley, David (dhurley@vet.uga.edu)-U of Georgia;
Czuprynski, Chuck (czuprync@svm.vetmed.wisc.edu)-U of Wisconsin;
Fulton, Robert (Robert.Fulton@okstate.edu)-Oklahoma State University
Briggs, Robert (bbriggs@nadc.ars.usda.gov)-USDA, ARS, National Animal Disease Center;
Chowdhury, Shafiqul (chowdh@vet.k-state.edu)-Kansas State University;
Daly, Russ (for Chris Chase) (Russell.daly@sdstate.edu)-South Dakota State University
Kousoulas, Gus ( VTGUSK@LSU.EDU)-Louisiana State University;

Brief Summary of Minutes

The meeting was opened with welcomes from Dr. Harry Dickerson, Associate Dean for Research and Graduate Affairs, College of Veterinary Medicine and Director, Veterinary Medical Experiment Station and Dr. Jerry Cherry, Associate Dean for Research, College of Agricultural and Environmental Sciences, and Director, Athens Agricultural Experiment Station. A brief history of college of Veterinary Medicine and Agricultural Experiment Station followed.

Business meeting:

Updates from the Administrative Advisor: Dr. Asem was unable to attend this meeting
He requested that the title and objectives for the new project covering 2006-2011 be submitted to the website following this meeting.

Future NC-107 meeting:
The group suggested that we may combine the future NC107 meeting with one of the following: (1). The Academy of Veterinary Consultants (beef and feedlot vets). (2). The AABP (mostly dairy, but also some beef vets). (3). The AAVLD (diagnostic Vets) or possibly but not as enthusiastically (4). CRWAD. Because there were only eight participants, it was decided that Dr. Chowdhury (Chair for next year) would send e-mail to every body and get the majority opinion. Because the attendance was low, there was a lengthy discussion about whether or not we should have a continued NC107 meeting. In the end, the consensus was that its a good group and we should not give up.

On September 14th (2nd day) the group worked on drafting/revising the objectives for the future NC-107 five year project.

New Station representative for Louisiana Dr. Gus Kousoulas was introduced.
Officers elected for 2006 were Chair, Dr. Shafiqul Chowdhury, Secretary, Dr. Robert Briggs.

Next meeting was left for the outcome of member input. Business Meeting closed on September 14, 2005 at 10:30 AM.

New business: The following were developed as the basis of the next project.
Title: An integrated approach to the control of bovine respiratory diseases

The objectives of the new project are:
(1). To evaluate the prevalence of viral and bacterial agents of respiratory disease by developing, validating and disseminating new state-of-the-art molecular diagnostics for rapid identification of these agents;


(2). To investigate the basic biology, molecular pathogenesis, and immunopathogenesis of polymicrobial infections including important viral and bacterial agents; and


(3). To develop management and prevention strategies that incorporate new vaccines and treatment protocols to combat bovine respiratory disease and reduce economic loss.


Station Reports were by the following:

Kansas Dr. Shafiqul Chowdhury
Louisiana Dr. Gus Kousoulas
Oklahoma Dr. Bob Fulton
South Dakota Dr. Russ Daly (for Dr. Chris Chase)
Wisconsin Dr. Chuck Czuprynski
USDA-NADC Dr. Bob Briggs
Georgia Dr. Amelia Woolums

Accomplishments

OBJECTIVE 1: Identify emerging and re-emerging agents and develop diagnostic methods for bovine respiratory disease (BRD).<br /> <br /> Oklahoma: Since 2003 we have tested samples from five feedyards in Oklahoma, Colorado, and Kansas to identify bovine viral diarrhea virus (BVDV) persistently infected (PI) cattle. There were 3463 samples tested with 116 positive (3.3%). The range of immunohistochemistry (IHC) positives in the five feedyards was 2.6% to 5.4%. In a recent shipment from one feedyard, 5.1% (8/157) were positive. This is about twice the rate for the past year. Vaccination histories and pen data for morbidity, mortality, treatment costs, number of treatments, and cost of gain are being collected for analysis. Such information will help communicate the adverse effects of PI cattle to feedlot management and ranchers supplying the cattle.<br /> <br /> BVDV subtypes in diagnostic lab accessions from clinical and necropsy cases, and the distribution of BVDV1a, 1b, and 2A subtypes, was evaluated. The prevalence of BVDV subgenotypes and biotypes was determined from 131 BVDV samples from a diagnostic laboratory. The BVDV samples were segregated into three subgenotypes by sequencing the 5-untranslated region (5UTR). There were 131 BVDV samples represented by 117 noncytopathic (NCP), 11 cytopathic (CP) and 3 cases with both biotypes. The NCP isolates were more common (P<0.05) than CP or NCP/CP. There were more BVDV1b subgenotypes 60/131 (45.8%) than BVDV1a, 37/131 (28.2%) or BVDV2a 34/131 (26.0%). All three subgenotypes were found in persistently infected (PI) cattle and respiratory diseases, both major requests for BVDV diagnosis. Only one of the 131 viruses was genetically similar to the strains in U.S. vaccines.<br /> <br /> Minnesota: The infectious agents associated with BRD were identified (7/04-6/05). 1. Bacteriology: Bacterial agents identified from bovine pneumonic lungs, nasal swabs, tracheal swabs, transtracheal fluids, and pleural swabs are as follows:<br /> Bacteria Isolations<br /> H. somnus 61<br /> M. haemolytica 69<br /> P. multocida 97<br /> Mycoplasma sp 72<br /> <br /> 2. Virology: Viral agents identified by different techniques are as follows: <br /> <br /> Virus FA IH PCR SN titers <8 Serum HI titers <40 Total<br /> IBR - 10 - 419 - 429<br /> PI3 - - - - 58 58<br /> BRSV - 17 - 110 - 127<br /> BVD - 2(tissues) 45(serum) - - 147<br /> 11(ear-89 (tissue<br /> skin) homogenate)<br /> <br /> BVD1 - - - 574 - 574<br /> BVD2 - - - 288 - 288<br /> BHV4 1 - - - - 1<br /> <br /> <br /> Wisconsin: Wisconsin Veterinary Diagnostic Laboratory provided the following data for the year 2004:<br /> <br /> Summary of WVDL Virology Results (1-01-04 to 12-31-04 ) <br /> 2004 #Tested #Positives % <br /> BVD PI serum 15,980 22 0.13% <br /> BVD-PI Buffy coat 1142 30 2.6 % <br /> BVD ear notch ELISA 24,422 144 0.58% <br /> BVD-BC acute 269 13 4.8%<br /> BVD serum ELISA 1633 11 0.67% <br /> Lung tissues VI-BVD 188 12 6.4% <br /> Lung tissues VI-IBR 188 1 0.53% <br /> FA Frozen section BVD lung 1215 37 3.0% <br /> FA Frozen section IBR lung 592 47 7.9% <br /> BRSV IHC positives 20 1 ** BRSV SN 474 361 ** <br /> PI3 3 0 0% <br /> <br /> Iowa: Work continues on the development and validation of ELISA serology methods to assess Mycoplasma bovis exposure. An ELISA test based on measuring sero-responses to an immunosuppressive peptide of M. bovis may allow differentiation of vaccinal responses from responses to infection.<br /> <br /> South Dakota: A. Diagnostic findings: The infectious agents associated with bovine respiratory disease complex were monitored (7/04-6/05): <br /> 1. Bacteriology: isolates from bovine pneumonic lungs, tracheal swabs, and nasal swabs are as follows:<br /> <br /> Organism Isolations<br /> M. haemolytica 80<br /> P. multicida 104<br /> H. somnus 63<br /> <br /> 2. Virology: Viral agents from bovine pneumonic lungs (455 isolation attempts): <br /> <br /> Virus Virus Isolations Fluorescent Antibody<br /> BVDV-NCP 23 <br /> BVDV-CP 13<br /> BHV-1 4 <br /> BRSV 0 19<br /> BHV-4 (DN-599) 8 <br /> <br /> <br /> 3. BVDV Genotyping: 79% of field isolates were BVDV type 2, 21% were type 1. <br /> 4. Immunoperoxidase BVDV outgrowth test for the detection of BVDV PI <br /> identified 5 positives of 7470. <br /> 5. Immunohistochemistry: IHC ear notch BVDV tests were conducted on 23,477 samples with 306 positives (1.3%). In 2004 there were 21,048 samples, 150 positives (0.7%). ELISA ear notch BVDV tests were conducted on 4,419 samples with 9 positives (0.2%). <br /> 6. Molecular Diagnostics: PCR tests were done for BVDV and 465 tests (3050 samples) were tested and 53 positives were detected. Typing was done on 91 PCR and VI isolates and 23% type 1 and 77% type 2. <br /> <br /> <br /> Georgia: The prevalence of Mycoplasma bovis in nasal swabs collected from cattle at arrival to backgrounding/stocker operations in Georgia was evaluated. In 9 operations, 87% of cattle were positive for mollicutes by PCR, while only 2% were positive for M. bovis. Fifteen percent were positive for any mycoplasma-type organism by culture, while 2% were positive for M. bovis by culture with PCR for specific identification. Thus herd level prevalence of M. bovis shedding was high but the animal-level prevalence was low, with between 2% - 6% of animals shedding on affected operations. <br /> <br /> Michigan: A rapid detection of BVDV in cell culture media using a biosensor has been demonstrated. Detection of cattle persistently infected with BVDV using ear notches was most consistent when compared to serum and nasal swabs. Further development may improve this tool for the rapid and economical identification of BVDV PI cattle.<br /> <br /> Bronchopneumonia continues to be the major cause of feedlot morbidity. The major pathogen associated with bronchopneumonia morbidity in Michigan appears to be Mycoplasma bovis. BVDV is often found in conjunction with M. bovis as well as other respiratory pathogens.<br /> <br /> NADC: Characterization of goat adenovirus isolates from Minnesota and Canada indicate that there may be across-species antigenic relationships among the ruminant Mastadenovirus, although they differ at the genetic level. Consensus primers for dependovirus and autonomous parvoviruses were developed to help characterize goat adenovirus/dependovirus isolates recovered from a recent outbreak to explore the their role in pathogenicity.<br /> <br /> Several widespread outbreaks of severe acute BVD have been traced to a single strain of BVDV. Unlike most strains which are low virulence this strain, which is high virulence, spread quickly from herd to herd and caused high mortality. This information is important to producers because the explosive spread of this virus suggests that these outbreaks must be controlled differently than typical outbreaks. We developed a research model that uses cultured cells rather that live animals to differentiate between high and low virulence viruses. This model will reduce the need to use live animals and will significantly cut the cost and difficulty of studying virulence in BVDV strains.<br /> <br /> <br /> <br /> OBJECTIVE 2: Characterize mechanisms and intervention targets in pathogenesis of BRD at the molecular, cellular, and host level.<br /> <br /> Minnesota: The site within the bovine CD18 required for LktA binding and its biological effects was mapped. We created bovine (B) x human (H) chimeric CD18 constructs by domain swapping the extracellular portion of human CD18 with corresponding sequences from the bovine CD18. The constructs were co-expressed with bovine CD11a in K562 cells, and resistance to LktA monitored. The results demonstrate that the binding site for LktA is contained within 500 to 600 amino acid residues of the extracellular region of bovine CD18. <br /> <br /> Mississippi: Integrated functional genomics was used to determine the effect of sub-lethal antibiotics on bacteria. Prophylactic use of antibiotics significantly reduces morbidity and mortality due to BRD. To determine the underlying mechanism of action of sub-minimum inhibitory concentrations (sub-MIC) of chlortetracycline (CTC) and CTC-sulfamethazine combination (CTC+SMZ), we compared the proteome of respiratory pathogen Mannheimia haemolytica grown in the presence of ¼ MIC of both antibiotic preparations to that obtained without the antibiotics. <br /> <br /> To analyze protein expression we used two dimensional liquid chromatography and in-line electospray ionization tandem mass spectrometry (2-D LC ESI MS2). When M. haemolytica was cultivated in the presence of ¼ MIC of CTC and CTC+SMZ, expression of 85 proteins was significantly altered by at least one treatment. The most notable sub-MIC effect was a significant decrease in the expression of leukotoxin A. Reduction in leukotoxin expression could be one of the molecular mechanisms responsible for the efficacy of these antibiotics. This finding provides a plausible explanation for the efficacy of prophylactic use of CTC in cattle.<br /> <br /> We showed that differential detergent fractionation (DDF) analysis of bovine monocytes reveals proteins related to antigen pattern recognition, uptake and presentation to immunocompetent lymphocytes. Recently, we have identified MR as the important receptor involved in endocytosis in bovine monocytes. We have also demonstrated that antigen uptake through MR-mediated endocytosis, an important APC function, is affected in monocytes in the early stage of BVDV infection during the first 24 hrs. In our research, we identified the following proteins related to antigen uptake: the galactose binding lectin, MyD-1, clathrin light chain A and MR precursor. We also identified 8 proteins related to cytoskeleton such as actin, beta actin and gamma actin. <br /> <br /> Wisconsin: How VP22 of BHV-1 enters the nucleus is unknown. No classic nuclear localization signal (NLS) motif has been identified. To identify the signal sequence directing nuclear accumulation, a series of truncations, internal deletions and point mutations were constructed. Evaluation of cells transfected with VP22 constructs indicated that a sequence of 103 residues is necessary and sufficient for nuclear localization. This sequence is conformation sensitive, in contrast to the classical sequential NLS. VP22 co-immunoprecipitated with histone H4, suggesting that interaction with histone H4 may contribute to the nuclear retention. <br /> <br /> We investigated intracellular pathways that result in bovine leukocyte death following exposure to M. haemolytica LKT. We find that LKT activates caspase-9 more than caspase-8, suggesting involvement of the mitochondrial pathway of apoptosis in LKT-mediated cell death. The anti-apoptotic protein Bcl-2 decreased, while the pro-apoptotic proteins Bax and Bad increased, following in vitro incubation of cells with LKT . Phosphorylation of Akt-1, a signaling protein downstream of LFA-1 that usually leads to cell survival, was decreased following LKT exposure. In addition we found evidence that the LKT is internalized, associates with actin stress fibers, makes it way to the mitochondria, and binds to the outer mitochondrial membrane. <br /> Mechanisms by which Haemophilus somnus causes the vasculitis that characterizes H. somnus infections were studied. We published evidence that H. somnus, but not its LOS, can cause platelet aggregation in vitro. H. somnus and its LOS, as well as H. somnus activated platelets, are capable of up-regulating tissue factor and ICAM-1 (CD54) and downregulating thrombomodulin on bovine pulmonary artery and brain microvascular endothelial cells, as determined by flow cytometry and Western blot. These changes may contribute to the vasculitis and thrombosis seen in H. somnus infections. <br /> The most severe manifestation of H. somnus infection is thrombomeningoencephalitis (TEM). Cerebral microvascular endothelial cells are the primary cellular constituent of the blood brain barrier, which protects the central nervous system from inflammation and infection. Using primary cell culture and Haemophilus somnus, we have developed an in vitro model to study the sequence of events and mediators involved in the dysfunction of the blood brain barrier in bacterial infection. We have investigated the ability of H. somnus to attach to and invade primary cerebral microvascular endothelial cells (CMVECs). Attachment occurs in a dose dependent manner, but invasion is rare. Binding of H. somnus to CMVECs appears to be inhibited by heparin, suggesting a role for glycosaminoglycans. CMVECs up-regulate TNF-£\, tissue factor, and ICAM-1 expression, and down-regulate the expression of occludin, a tight junction protein, following exposure to H. somnus. CMVECs exposed to H. somnus also undergo apoptosis. These alterations could play a role in the development of vasculitis, thrombosis and inflammation that results in blood brain barrier dysfunction and bacterial invasion of the brain <br /> <br /> South Dakota: Two new molecular tools, toll like receptor (TLR) 2 and 4 real time PCR assays, were developed for molecular pathogenesis studies. Monocyte-derived macrophages (MDM) were infected with BVDV strains of different virulence. mRNA for TLR-2 and -4 of virus-infected MDMs was quantified by RT-PCR using molecular beacons. After 12 hrs of infection, a BVDV strain from persistent infection significantly (p<0.05) decreased the amount of TLR-2 mRNA as compared to the mock and other strains. However, this virus has only minimal effect on TLR-4 mRNA Thus, BVDV may modify the innate immune recognition by influencing the expression of toll-like receptors. <br /> <br /> Thirty-nine calves from a single farm were transported to a university facility in September 2004. Subsequent testing revealed that 36 of the animals were PI with BVDV type 2a. These animals were analyzed over a 10-month period for virological and serological changes. NCP-BVDV was isolated from all the calves and the 5 UTR and E2 region were analyzed. The results indicate that the 5UTR was similar among all calves but one group of 7 calves had conserved changes in the E2 region. Twenty-four of the calves succumbed to mucosal disease during the experiment and CP-BVDV virus was isolated from 18 calves. The CP-BVDV is currently being sequenced to determine mutation differences. Six of the PI animals developed SN titers against both type 1 and type 2 calves. There was no relationship between the development of antibody and onset of mucosal disease. These results indicate that within a population of PI infected animals that the amount of genetic variation in the 5UTR and E2 that occurs over time is well conserved and that small variations in E2 region can occur within the same cohort but these changes occur very early in the infection.<br /> <br /> The infectivity of BVDV white deer isolates in white tailed deer was evaluated. Eight white tailed deer fawns 4-6 weeks in age were placed in 2 groups: group 1 was inoculated with non-cytopathic (NCP) BVDV type 1b, and group 2 was inoculated with NCP-BVDV type 2. A control group of two animals was also used. The two viruses were recovered in the fall of 2004 from two separate cases of unthrifty deer in South East South Dakota. The deer were negative for chronic wasting disease but were positive for BVDV by IHC and virus isolation. Virus was administered through oral and nasal routes. Clinical observations were recorded daily from -3 to 13 days post-inoculation. Average body temperatures were significantly elevated in the infected animals on day 6 for group 1 and day 7 for group 2. Average lymphocyte count for each group was <50% of control for 1 day within each group, 43% on day 3 for group 1 and 47% on day 6 for group 2. White tail deer are susceptible to BVDV infection from white tail deer isolates. It remains to be determined if deer can transmit the virus to cattle or if deer can become persistently infected as calves <br /> <br /> Georgia: To characterize management practices related to feedlot acute interstitial pneumonia (AIP), a survey was sent to managers at 561 U.S. feedlots in 21 states. Of 72 surveys returned (12.8%), 53% came from Kansas and Nebraska. The total number of cattle placed by respondents was 2,495,439, representing approximately 10% of the cattle placed in 2000. Vaccination for viral respiratory pathogens was common; fewer feedlots vaccinated for Haemophilus somnus or Pasteurella (Mannheimia). 61% of respondents practiced metaphylactic administration of antimicrobials. 65% of animals that died received a postmortem examination; 16% of respondents reported that no animals received postmortems. BRD was the leading cause of morbidity and mortality; 12.8% of placements were treated for BRD and 0.8% were died due to BRD. Of all placements, 1.3% of cattle were treated for AIP and 0.1% of placements died of AIP. Managers reported that 80.5% of AIP deaths occurred in cattle on feed over 60 days, 62% of AIP deaths occurred in the summer, and 62.2% of AIP deaths were heifers. Thirty-three feedlots reported the percent of placements that died of AIP (0.001-0.75%). Feedlots in northern states were less likely to report AIP as a cause of morbidity/mortality, while larger feedlots and feedlots placing higher proportions of yearlings more often recognized AIP as a cause of morbidity/mortality. Although heifers were recognized to account for 62% of AIP deaths, feedlots placing a large proportion of heifers were not more likely to recognize AIP as a cause of morbidity/mortality. Feedlots that vaccinated over 95% of cattle for Mannheimia/Pasteurella were less likely to recognize AIP as a cause of morbidity/mortality. <br /> <br /> NADC: ARS scientists have developed a method for isolation of respiratory tract dendritic cells from ruminant lung tissue. Respiratory tract dendritic cells were isolated using a magnetic-activated cell sorter (MACS). Following MACS purification, the cells were examined by electron microscopy and by flow cytometry for dendritic cell-specific surface molecules and tracer endocytosis. During this past year, dendritic cells have been isolated from neonatal lambs as well as adult sheep. This is the first documented isolation of dendritic cells from neonatal animals. Pulmonary dendritic cells from neonates and adults are similar phenotypically and functionally. This is in contrast to the current dogma that suggests that neonatal dendritic cells are less mature.<br /> <br /> Nebraska: BVDV has a 12.5 kb, single-stranded RNA genome consisting of a 5 untranslated region (UTR), a single large open reading frame and a 3 UTR. The 5 UTR contains an internal ribosomal entry site (IRES) necessary for translation in a cap-independent manner. Bovine viral diarrhea virus genotype 2 (BVDV2) isolates have a wide range of virulence. We have determined that in BT and BL-3 cells, the Npro coding region either had no influence or caused a significant decrease in IRES-mediated translational efficiency, with the exception of BVDV 890. Mutagenesis of IRES base 219 and/or 278 ameliorated suppression of the translational efficiency. Results suggest interactions between the Npro and nucleotides within and external to the IRES element influence translational efficiency. These results underscore the complex interplay of cellular factors influencing IRES-mediated translation. These constructs will be useful in continued studies using an infectious full-length BVDV2 clone to characterize the interplay of the IRES and the Npro coding region of BVDV2 on virulence.<br /> <br /> Vaccination against BVDV infection should protect against viremia and prevent dissemination of virus throughout the host, blocking infection of target cells. The objective of this study was to characterize the protection against infection and disease from challenge exposure with NY-1 BVDV afforded by use of a MLV noncytopathic BVDV type 1 vaccine. Vaccine virus replicated systemically in vaccinated calves as evident antemortem by decreased peripheral leukocyte and lymphocyte counts, and postmortem by lymphoid depletion in Peyers patches and mesenteric lymph nodes. Post-challenge, nonvaccinated calves developed clinical signs of disease, viremia, leukopenia, and thymic infection. In contrast, post-challenge, vaccinated calves did not exhibit fever, signs of respiratory tract disease, leukopenia, or viremia.<br /> <br /> BHV latency: We have previously demonstrated that the LR gene encodes a protein that is expressed in sensory neurons and during productive infection. Site-directed mutagenesis indicated that ORF-2 expression is required for the latency-reactivation cycle of BHV-1. The LR gene interferes with apoptosis, which promotes neuronal survival during the transition from acute infection to latency. LR-RNA sequences or a small open reading frame appears to inhibit bICP0 expression (the gene that is anti-sense to the LR gene), and consequently can inhibit viral gene expression. We believe that the LR gene encodes multiple functions that cooperate to regulate latency. The dominant function is a protein encoded by ORF-2 that is absolutely required for the latency-reactivation cycle in cattle. The LR gene also plays a role in the ability of BHV-1 to grow in the tonsils of infected calves. LR mutant virus can persist in the tonsils of latently infected calves, but it does not reactivate from latency. Studies that are in progress now to compare viral gene expression in TG or tonsils of calves latently infected with wt BHV-1 or the LR mutant.<br /> <br /> Analysis of the bICP0 gene: bICP0 is considered to be most important transcriptional regulatory gene of BHV-1. In addition to regulating transcription, bICP0 is toxic to cells. bICP0 contains a C3HC4 zinc RING finger at its amino terminus. Site-specific mutagenesis on the C3HC4 zinc RING finger revealed this domain is necessary for toxicity and eliminates transcriptional regulatory activity. Since bICP0 does not specifically bind DNA, we hypothesized that bICP0 interacts with transcription factors. Earlier studies have demonstrated that bICP0 interacts with histone deacetylase 1 (HDAC1). HDAC1 represses transcription because it removes acetyl groups from histones, thus making chromatin transcriptionally inactive. To identify bICP0 functional domains that are not part of the zinc RING finger, we developed a panel of transposon insertion mutants that span bICP0. A large domain spanning amino acids 78-256, and a separate domain that is at or near amino acid 457 was necessary for efficient trans-activation of a promoter. Sequences near the C-terminus (amino acids 607-676) contain a functional nuclear localization signal (NLS). Collectively, our studies indicated that bICP0 contains several important functional domains; 1) the zinc RING finger, 2) two separate domains that activate transcription, and 3) a C-terminal NLS that is also necessary for efficient trans-activation. <br /> <br /> Kansas: We examined the role of envelope proteins gE and US9 in the anterograde transport of BHV-1 following reactivation in TG neurons of calves. Nasal and ocular virus shedding was quantitated by plaque assay during primary infection and after reactivation. During primary infection, calves infected with BHV-1 wild type, gE deleted, or US9 deleted recombinant viruses shed similar amounts of virus from the eye and nasal cavity. When reactivation was initiated with dexamethasone, virus shedding was observed only in calves infected with wild type virus, but not in gE and US9-deleted BHV-1 viruses. The establishment of latent infection in TG neurons by these three viruses was determined by quantitating the latent genomic copy numbers by real time PCR using gB specific primer pairs and probe. The latent genomic copy numbers for all the three viruses were comparable. These results indicate that the US9 and gE-deleted BHV-1 recombinant viruses infect, grow and establish latency following infection similar to wild type virus but are not transported to the nasopharynx and eye following reactivation. gE and US9 may play a role in anterograde transport from TG neurons back to the nasal epithelium, cornea and conjunctiva. <br /> <br /> <br /> <br /> OBJECTIVE 3: Develop intervention strategies for critical control points to reduce the impact of BRD.<br /> <br /> Minnesota: We have demonstrated previously that the beta2 integrin LFA-1 is a receptor for LktA in bovine leukocytes and is involved in leukotoxin-induced biological effects. However the subunits within LFA-1 involved in binding and post-binding signaling have not been well characterized. Our research precisely pinpointed and characterized the interaction of the LFA-1 subunits with LktA. The results indicate that although LktA can efficiently bind to the CD18 subunit of both LFA-1 and Mac-1, post-binding signaling events including elevation of intracellular calcium and CD18 tail phosphorylation are only observed through LFA-1. Furthermore, LktA also binds to the CD11a subunit of LFA-1. LktA binding to CD11a could be inhibited by a small molecule inhibitor of the I- domain, the major ligand binding site on CD11a. These results suggest that CD18 subunit of bovine LFA-1 contains the LktA binding site and signaling through LFA-1 requires LktA interaction with the I-domain of CD11a, and this binding is critical in bringing about intersubunit interaction resulting in signaling. This is the first report which describes discrete functions for the CD18 and CD11a subunits in the LFA-1/LktA interaction in bovine leukocytes. <br /> <br /> Oklahoma: During the fall 2003 and winter 2004 there were reports of BHV-1 disease in cattle with prior vaccination with MLV vaccines. These episodes occurred 50 or more days after arrival/processing, and were not associated with any one vaccine. We determined if field isolates from these cases were susceptible to the BHV-1 antibodies in MLV vaccinated calves. Results of this study using 5 vaccine strains, a reference BHV-1 Colorado NVSL strain, BHV-1 Cooper challenge strain, and an isolate from a clinic case indicated a wide range of antibody titers when vaccinated calves serum were tested against these 8 strains. The titers were highest to the BHV-1 Colorado NVSL and one MLV vaccine virus (Baker strain). The lowest titers were to the BHV-1 Cooper challenge strain and the recent field strain, BHV-1-31751. In almost all sera, the differences were 3-10 fold less. Interestingly, the antibody titers in the calves serums were quite low to the homologous vaccine. It appears that most of the vaccines induced antibodies that poorly neutralized the BHV-1 Cooper challenge strain and the field strain.<br /> <br /> Wisconsin: The relationships between air quality, a variety of environmental risk factors, and calf respiratory health in 13 naturally ventilated calf barns was evaluated. A minimum of 12 pre-weaned calves were randomly selected and scored for the presence of respiratory disease at each site. An air sampling device was used to determine airborne bacteria colony forming units per cubic meter (cfu/m3) of air in calf pens and central alleys within the barns. Temperature and relative humidity were recorded in each calf pen, the barn alley, and outside the barn. Pen bedding type, dry matter, and a calf nesting score were recorded. Significant factors associated with reduced exterior wind speed and direction were determined and used to estimate building ventilation rates. Factors that were significantly associated with a reduced prevalence of respiratory disease were reduced pen log10 cfu/m3, presence of a solid barrier between each calf, different pen, and increasing nesting score. Significant factors associated with reduced alley log10 cfu/m3 were increased ventilation changes per hour, increased barn volume per kg of calf, reduced pen log10 cfu/m3, and barn type. <br /> <br /> Iowa: A survey of antimicrobial susceptibility of 223 recently recovered isolates of Mycoplasma bovis from across the U.S was completed by broth microdilution. There were no significant differences in susceptibility patterns related to geographic origin or disease presentation. Enrofloxacin, florfenicol, and spectinomycin were found to be active. Oxytetracycline and chlortetracycline were active against half the isolates; very few isolates were susceptible to tilmicosin. None were susceptible to erythromycin, ampicillin, or ceftiofur.<br /> <br /> Kansas: Needle-free and conventional needle-andsyringe injection techniques were evaluated in two studies of dairy calves and feedlot steers. Study 1: 104, 5- to 10-month old Holstein calves were vaccinated with 5-way MLV virus vaccine, Mannheimia haemolytica bacterin-toxoid and 5-way Leptospira bacterin using needle-free or conventional injection. The serological response to the IBR fraction of the 5-way viral vaccine and MH bacterin was significantly higher for the needle-free route of administration, while the serological response to the LP fraction was not significantly different. Study 2: 111 yearling feedlot steers were vaccinated with 5-way modified-live virus vaccine and Mannheimia haemolytica (MH) bacterin-toxoid, using needle-free or conventional injection. Serological response to the IBR viral fraction of the 5-way vaccine was significantly higher (P=0.001) on day 21 following needle-free injection, compared to conventional injection. Serological responses to the MH supernatant and cell-associated antigens were not statistically different.<br /> <br /> Louisiana: Research indicated that the antimicrobial peptide cecropin B is effective in inhibiting M. haemolytica colonization in the nasal passage of calves. Transfection of the upper respiratory tract with 100 ¼g of plasmid DNA per nostril inhibited colonization of a virulent strain of M. haemolytica S1 as long as 14 days after transfection. <br /> <br /> The spike glycoproteins encoded by two prototypic respiratory and enteric bovine coronaviruses were codon optimized. This codon optimization resulted in high gene expression in transient assays as compared to wild type genes.<br /> <br /> NADC: New leukotoxin mutants of M. haemolytica serotypes 1 and 6 were constructed which express and transport the C-terminal 1/3 of the leukotoxin structural gene and which may be useful for vaccination. The larger deletion introduced into the new mutants may reduce adverse reactions in Bighorn sheep. <br /> Adenoviruses appear to play a role in outbreaks of respiratory disease in domestic and wild ruminants. Additional work is necessary to characterize their role to design effective strategies for disease intervention.<br /> <br /> <br /> <br /> <br /> INTER-STATION COLLABORATIVE EFFORTS<br /> <br /> SD, NE, OK and AL collaborated on an issue of Veterinary Clinics of North America focused on bovine viral diarrhea virus<br /> <br /> MI worked with SD, KS, OK, AL, OH and NADC in identifying cattle persistently infected with BVDV for natural fetal challenge study.<br /> <br /> SD, GA, CA, and NE collaborated on BRSV challenge models<br /> <br /> SD, AL, MI, and NADC shared various BVDV strains and collaborated on developing new challenge models.<br /> <br /> SD and GA collaborated on bovine immunology studies.<br /> <br /> SD shared BHV-1 strains with KS, U of Pennsylvania and Princeton.<br /> <br /> GA collaborated with University of Montreal and NIH on new vaccine vehicles and delivery systems.<br /> <br /> GA collaborated with Merial in measuring vaccine efficacy across a multi assay platform.<br /> <br /> KS and NE shared reagents related to BHV-1 and BHV-5 research.<br /> <br /> CA shared BRSV isolates with SD and U of Tennessee.<br /> <br /> NADC and OK in constructing and evaluating new mutant P. multocida vaccine.<br /> <br /> NADC, OK and New Mexico State on evaluating mucosal immunity to oral M. haem/P. multi vaccine<br /> <br /> NADC and MN collaborated on generating leukotoxin knock out mutants of M. haemolytica.<br /> <br /> NADC, NE, OK, WI and MN share monoclonal antibodies directed against M. haemolytica leukotoxin.<br /> <br /> OK and NADC collaborated on sequencing of multiple BVDV isolates.<br />

Publications

PEER-REVIEWED PUBLICATIONS:<br /> <br /> Rosenbusch, R. F., Kinyon, J. M., Apley, M., Funk, N. D., Smith, S., and L. J. Hoffman. In vitro antimicrobial inhibition profiles of Mycoplasma bovis isolates recovered from various regions of the United States from 2002-2003. (In Press, J. Vet Diagn. Invest.).<br /> <br /> <br /> Lu, X., and R. F. Rosenbusch. 2004. Endothelial cells from bovine pulmonary microvasculature respond to Mycoplasma bovis preferentially with signals for mononuclear cell transmigration. Molecular Pathogenesis 37: 253-261.<br /> <br /> <br /> Nanduri, B., M. L. Lawrence, and S. C. Burgess. In press. Proteomic analysis using an unfinished bacterial genome: the effects of sub-minimum inhibitory concentrations of antibiotics on Mannheimia haemolytica virulence factor expression. Proteomics.<br /> <br /> <br /> Reeks, B. Y., F. R. Champlin, D. B. Paulsen, D. W. Scruggs, and M. L. Lawrence. 2005. Effects of sub-MIC antibiotic levels and temperature on growth kinetics and outer membrane protein expression in Mannheimia haemolytica and Haemophilus somnus. Can. J. Vet. Res. 69:1-10.<br /> <br /> <br /> Boyd, B. L., Lee, T. M., Kruger, E. F., Pinchuk, L. M . 2004. Cytopathic and Noncytopathic Bovine Viral Diarrhoea Virus Biotypes affect Fluid Phase Uptake and Mannose Receptor-Mediated Endocytosis in Bovine Monocytes. Vet. Immunol. Immunopathol. 102:53-65.<br /> <br /> <br /> S.-R. Lee, G. T. Pharr, A. M. Cooksey, F. M. McCarthy, B. L. Boyd, and L. M. Pinchuk. Differential detergent fractionation for non-electrophoretic bovine blood monocyte proteomics reveals proteins involved in professional antigen presentation. In preparation.<br /> <br /> <br /> Klink H.A, R.P. Brady, C. L.Topliff, K.M. Eskridge, S. Srikumaran, C. L. Kelling. 2005. Influence of bovine respiratory syncytial virus F glycoprotein N-linked glycans on in vitro expression and on antibody responses in BALB/c mice. Vaccine. Accepted for publication.<br /> <br /> <br /> Kelling, C. L., B.D. Hunsaker, D.J. Steffen, 2005. Characterization of protection in experimentally-infected calves from systemic infection or disease by vaccination with modified-live noncytopathic bovine viral diarrhea virus type 1. American Journal of Veterinary Research. Accepted for publication.<br /> <br /> <br /> Topliff CL, Chon SK, Donis RO, Eskridge KM, Kelling CL. 2005. In vitro and in vivo translational efficiencies of 5' untranslated region from eight genotype 2 bovine viral diarrhea virus isolates. Virology 331: 349-356.<br /> <br /> <br /> Achenbach JE, Topliff CL, Vassilev VB, Donis RO, Eskridge KM, Kelling CL. 2004. Detection and quantitation of bovine respiratory syncytial virus using real-time quantitative RT-PCR and quantitative competitive RT-PCR assays. Journal of Virological Methods 121: 1-6.<br /> <br /> <br /> Brady RP, Topliff CL, Kelling CL. 2004. In vitro expression of full-length and truncated bovine respiratory syncytial virus G proteins and their antibody responses in BALB/c mice. Vaccine 22: 3762-3768.<br /> <br /> <br /> Henderson, G., G.-C. Perng, A. B. Nesburn, S. L. Wechsler, and C. Jones. 2004. The latency related (LR) gene encoded by bovine herpesvirus 1 (BHV-1) can suppress caspase 3 and caspase 9 cleavage during productive infection. J. of Neurovirology. 10:64-70.<br /> <br /> <br /> Jiang, Y., M. Inman, Y. Zhang, N. A. Posadas , and C. Jones. 2004. A mutation in the latency related gene of bovine herpesvirus 1 (BHV-1) inhibits expression of proteins encoded by ORF2 and Reading Frame C during productive infection. J. of Virology 78:3184-3189. <br /> <br /> <br /> Inman, M., J. Zhou, H. Webb, and C. Jones. 2004. Identification of a novel transcript containing a small open reading frame that is expressed during latency, and is antisense to the latency related gene of bovine herpes virus 1 (BHV-1). J. of Virology 78:5438-5447.<br /> <br /> <br /> Henderson, G., Y. Zhang, M. Inman, D. Jones and C. Jones. 2004. Infected cell protein 0 encoded by bovine herpesvirus 1 can activate caspase 3 when overexpressed in transfected cells. J Gen Virol ; 85: 3511-3516<br /> <br /> <br /> Perez, S., M. Inman, A. Doster, and C. Jones. 2005. The latency related gene encoded by bovine herpesvirus 1 (BHV-1) promotes virus growth and reactivation from latency in tonsils of infected calves. J. of Clinical Microbiology. 43: 393-401.<br /> <br /> <br /> Zhang, Y. and C. Jones. 2005. Identification of functional domains within the bICP0 protein encoded by BHV-1. J. of General Virology, 86:879-886.<br /> <br /> <br /> Geiser, V., Y. Zhang, & C. Jones. 2005. Analysis of a bovine herpesvirus 1 (BHV-1) recombinant virus that does not express the bICP0 protein. J. of General Virology. 86: 1987-1996.<br /> <br /> <br /> Confer, A.W., Fulton, R.W., Step, D.L., Johnson, B.J., Ridpath, J.F.: Viral Antigen Distribution in the Respiratory Tract of Cattle Persistently Infected with Bovine Viral Diarrhea Virus Subtype 2a. Veterinary Pathology, 42:192-199, 2005.<br /> <br /> <br /> Step, D.L, Confer, A.W., Kirkpatrick, J.G., Richards, J.B., Fulton, R.W.: Respiratory Tract Infections in Dairy Calves from Birth to Breeding Age: Detection by Laboratory Isolations and Seroconversions. Bovine Practitioner, 39:44-532, 2005.<br /> <br /> <br /> Fulton, R.W., Briggs, R.E., Ridpath, J.F., Saliki, J.T., Confer, A.W., Payton, M.E., Duff, GC, Step, D.L., Walker, D.: Transmission of Bovine Viral Diarrhea Virus 1b to Susceptible and Vaccinated Calves by Exposure to Persistently Infected Calves. Canadian Journal for Veterinary Research, 69:161-169, 2005.<br /> <br /> <br /> Welsh RD, Dye LB, Payton ME, Confer AW. Frequency of isolation and antimicrobial susceptibilities of bacterial pathogens from bovine pneumonia: 1994-2002. J Vet Diag Invest 16:426-431, 2004.<br /> <br /> <br /> Ayalew S, Confer AW, Blackwood ER. Characterization of Immunodominant and Potentially Protective Epitopes of Mannheimia haemolytica Serotype 1 Outer Membrane Lipoprotein PIpE. Infect and Immun 72:7265-7274, 2004.<br /> <br /> <br /> Prado ME, Dabo SM, Confer AW. Immunogenicity of iron-regulated outer membrane proteins of Pasteurella multocida A:3 in cattle: molecular characterization of the immunodominant heme acquisition system receptor (HasR) protein. Vet Microbiol, 105:269-280, 2005.<br /> <br /> <br /> Carter JN, Gill DR, Lalman DL, Krehbiel CR, Confer AW, Smith RA, Claypool PL, McDowell LR. Vitamin E supplementation in the diet of newly arrived feedlot cattle. J Anim Sci 83:1924-1932, 2005.<br /> <br /> <br /> Thumbikat, P., T. Dileepan, M.S. Kannan and S.K. Maheswaran. 2005. Mechanisms underlying Mannheimia haemolytica leukotoxin-induced oncosis and apoptosis of bovine leukocytes. Microbial Pathogenesis 38: 161-172.<br /> <br /> <br /> Dileepan, T., P. Thumbikat, B. Walcheck, M.S. Kannan, and S.K. Maheswaran. 2005. Recombinant expression of bovine LFA-1 and characterization of its role as the receptor for Mannheimia haemolytica leukotoxin. Microbial Pathogenesis 38: 249-257.<br /> <br /> <br /> Thumbikat, P., T. Dileepan, M.S. Kannan and S.K. Maheswaran. 2005. Characterization of Mannheimia (Pasteurella) haemolytica leukotoxin interaction with bovine alveolar macrophage b2 integrins. Veterinary Research. September Issue.<br /> <br /> <br /> Dileepan, T., M.S. Kannan, B. Walcheck, P. Thumbikat, and S.K. Maheswaran. 2005. Mapping of the binding site for Mannheimia haemolytica leukotoxin within the bovine CD18. Infection and Immunity. 73: 5233-5237.<br /> <br /> <br /> Fairbanks KK, CL Rinehart, WC Ohnesorge, MM Loughin and CCL Chase. 2004. Evaluation of fetal protection against experimental infection with type 1 and type 2 bovine viral diarrhea virus after vaccination of the dam with a bivalent modified-live virus vaccine. JAVMA 225:1898-2004<br /> <br /> <br /> Al-Mubarak, A. and Chowdhury, S.I.. Glycoprotein I (gI)-deleted BHV-5 retains significant neurovirulence. 2004. J. Neurovirology 10:233-243.<br /> <br /> <br /> Hollis LC, Smith JF, Johnson BJ, Kapil S, Mosier DA: A Comparison of Serological Responses when Modified-live Infectious Bovine Rhinotracheitis Virus Vaccine, Mannheimia haemolytica Bacterin-Toxoid are Administered with Needle-free versus Conventional Needle-based Injection in Yearling Feedlot Steers. 2005. The Bovine Practitioner 39:106-109. <br /> <br /> <br /> Hollis LC, Smith JF, Johnson BJ, Kapil S, Mosier DA: A Comparison of Serological Responses when Modified-live Infectious Bovine Rhinotracheitis Virus Vaccine, Mannheimia haemolytica Bacterin-Toxoid and Leptospira pomona Bacterin are Administered with Needle-free versus Conventional Needle-based Injection in Holstein Dairy Calves. 2005. The Bovine Practitioner. 39:110-114.<br /> <br /> <br /> Dunn J, Kaneene JB, Grooms D, Bolin S, Bolin C, Bruning-Fann C. Effects of positive results for Mycobacterium avium subsp paratuberculosis as determined by microbial culture of feces or antibody ELISA on results of caudal fold tuberculin test and interferon-gamma assay for tuberculosis in cattle. American Journal of Veterinary Research, 2005;226:429-435<br /> <br /> <br /> Tahir ZM, Alocilja EC, Grooms DL. Polyaniline synthesis and its biosensor application. Biosens Bioelectron. 2005;15;20(8):1690-1695.<br /> <br /> <br /> Boudreaux, C.M., Corstvet, R.E., Cooper, R.K., and Enright, F.M., 2005. Effects of cecropin B transgene expression on Mannheimia haemolytica serotype 1 colonization of the nasal mucosa of calves. A J Vet Res. In Press.<br /> <br /> <br /> Chad M Petit; Jeffery M Melancon ; Vladimir N Chouljenko; Robert C Colgrove; Michael Farzan; David M Knipe; Konstantin Kousoulas. 2005. Genetic Analysis of the SARS-Coronavirus Spike Glycoprotein Functional Domains Involved in Cell-Surface Expression and Cell-to-Cell Fusion (Virology; In press).<br /> <br /> <br /> <br /> Doyle, C.K., Labruna, M.B., Breitschwerdt, E.B., Tang, Y, Corstvet, R.E., Hergarty, B.C., Bloch, K.C., Li, P., Walker, D.H., and McBride, J.W., 2005. Detection of medically important Ehrlichia by quantitative multicolor TaqMan real-time polymerase chain reaction of the dsb gene. J Mol Diagn 7(4):1-7.<br /> <br /> <br /> Vladimir N Chouljenko, Chad M. Petit and K. G. Kousoulas. Delineation of functional domains of the spike glycoprotein encoded by enteric and respiratory strains of bovine coronavirus (In preparation). <br /> <br /> <br /> Woolums AR, Loneragan GH, Hawkins LL, Williams SM. Baseline management practices and animal health data reported by U.S. feedlots responding to a survey regarding acute interstitial pneumonia. Bov Pract, 39:116-124; 2005.<br /> <br /> <br /> Woolums AR, Loneragan GH, Hawkins LL, Williams SM. A survey of the relationshiop between management practices and risk of acute interstitial pneumonia at U.S. feedlots. Bov Pract; 39:125-133; 2005.<br /> <br /> <br /> Reber, AJ, Hippen, AR, Hurley, DJ, 2005. Ingestion of whole colostrum rapidly induces the capacity in newborn calves to stimulate and respond in one-way mixed leukocyte cultures. AJVR (in Press). <br /> <br /> <br /> Briggs, R. E., Tatum, F. M. Generation and molecular characterization of new temperature-sensitive plasmids intended for genetic engineering of the Pasteurellaceae. Appl. Environ. Microbiol. Accepted July 19, 2005.<br /> <br /> <br /> <br /> Briggs, R. E., Tatum, F. M. Construction of Pasteurella haemolytica vaccines. U.S. Patent 6,793,927 issued September 21, 2004.<br /> <br /> <br /> Fulton, R. W., Briggs, R. E., Ridpath, J. F., Saliki, J. T., Confer, A. W., Payton, M. E., Duff, G. C., Step, D. L, Walker, D. Transmission of bovine viral diarrhea virus 1b to susceptible and vaccinated calves by exposure to persistently infected calves. Can J Vet Res. 2005; 69:161-169.<br /> <br /> <br /> Meyerholz DK, Grubor B, Gallup JM, Lehmkuhl HD, Anderson RD, Lazic T, Ackermann MR. Adenovirus-mediated gene therapy enhances parainfluenza virus 3 infection in neonatal lambs. J Clin Microbiol. 2004 Oct;42(10):4780-7.<br /> <br /> <br /> Meyerholz DK, Grubor B, Fach SJ, Sacco RE, Lehmkuhl HD, Gallup JM, Ackermann MR. Reduced clearance of respiratory syncytial virus infection in a preterm lamb model. Microbes Infect. 2004 Nov;6(14):1312-9. <br /> <br /> <br /> Tatum, F. M., Yersin, Y. G., Briggs, R. E. Construction and virulence of a Pasteurella multocida FhaB2 mutant in turkeys. Microb Pathog. 2005 Jul-Aug;39(1-2):9-17.<br /> <br /> <br /> Tatum, F. M., Briggs, R. E. Construction of in-frame aroA deletion mutants of Mannheimia haemolytica, Pasteurella multocida, and Haemophilus somnus using a new temperature-sensitive plasmid. Appl. Environ. Microbiol. Accepted July 19, 2005.<br /> <br /> <br /> Atapattu, D. and C.J. Czuprynski. 2005. Mannheimia haemolytica leukotoxin induces apoptosis of bovine lymphoblastoid cells (BL-3) via a caspase-9 dependent mitochondrial pathway. Infect. Immun. (in press). <br /> <br /> <br /> Kuckleburg, C., M.J. Sylte, T. J. Inzana, L.B. Corbeil, B. Darien and C.J. Czuprynski. 2005. Bovine platelets activated by Haemophilus somnus or its lipooligosaccharide cause endothelial cell damage in vitro. Microb Pathogen. 38:23-32. <br /> <br /> <br /> Lago, A., S.M. McGuirk, T.B. Bennett,, N.B. Cook,, and K. V. Nordlund. Submitted. Calf respiratory disease and pen microenvironments in naturally ventilated calf barns in winter. J. Dairy Sci. <br /> <br /> <br /> Leite, F., D. Atapattu, C. Kuckleburg, , R. Schultz, and C.J. CZUPRYNSKI. 2004. Incubation of bovine PMNs with conditioned medium from BHV-1 infected peripheral blood mononuclear cells increases their susceptibility to Mannheimia haemolytica leukotoxin. Vet. Immunol. Immunopathol. 103:187-193. <br /> <br /> <br /> Qiu, Z., J. S. Harms, J. Zhu, and G. A. Splitter. 2004. Bovine herpesvirus tegument protein VP22 enhances thymidine kinase/Ganciclovir suicide gene therapy for neuroblastomas compared to herpes simplex virus VP22. J. Virol. 78:4224-4233. <br /> <br /> <br /> Qiu Z, Zhu J, Harms JS, Friedrichsen J, Splitter GA. 2005. Bovine herpesvirus VP22 induces apoptosis in neuroblastoma cells by upregulating the expression ratio of Bax to Bcl-2. Hum Gene Ther. 16:101-108. <br /> <br /> <br /> Slack, J., Thomas, C and Peek, S.F. 2004. Pneumothorax in dairy cattle : 30 cases (1990-2003). J. Amer. Vet. Med. Assoc. 225:732-735. <br /> <br /> <br /> Sylte, M.J., C. J. Kuckleburg, L. B. Corbeil, T. J. Inzana, P. J. Bertics, and C. J. Czuprynski. 2005. Stimulation of P2X7 enhances Haemophilus somnus lipooligosaccharide-mediated apoptosis of endothelial cells. J. Leuk. Biol. 77:958-965. <br /> <br /> <br /> Sylte, M.J. C. J. Kuckleburg, F.P. Leite, T.J. Inzana and C.J. CZUPRYNSKI. 2005. Interleukin-1 beta diminishes Haemophilus somnus lipooligosaccharide-mediated apoptosis of endothelial cells. Microb. Pathogen. (in press). <br /> <br /> <br /> Sylte, M., T. Inzana and C. J. CZUPRYNSKI. Submitted. Role of tumor necrosis factor in endothelial cell apoptosis caused by Haemophilus somnus lipooligosaccharide. Vet. Immunol. Immunopathol. <br /> <br /> <br /> Zhu J, Z. Qiu, C. Wiese, Y. Ishii, J. Friedrichsen, G. Rajashekara, and G.A. Splitter. 2005. Nuclear and mitochondrial localization signals overlap within bovine herpesvirus 1 tegument protein VP22. J. Biol. Chem. 280:16038-16044. <br /> <br /> <br /> <br /> ABSTRACTS:<br /> <br /> <br /> Nanduri, B., S. C. Burgess, and M. L. Lawrence. 2005. Sub-MIC concentrations of antibiotics decrease Mannheimia haemolytica leukotoxin expression. 105th General Meeting of the American Society for Microbiology, Atlanta, Georgia.<br /> <br /> <br /> Nanduri, B., M. L. Lawrence, and S. C. Burgess. 2005. Proteomic profiling of M. haemolytica; a bacterial pathogen with a draft genome. 53rd ASMS Conference on Mass Spectrometry, San Antonio, Texas.<br /> <br /> <br /> Lawrence, M. L. 2005. Impact of sub-MIC levels of chlortetracycline and chlortetracycline/ sulfamethazine on growth kinetics of Mannheimia haemolytica and Haemophilus somnus. Summer 2005 Academy Of Veterinary Consultants Conference, Kansas City, Missouri.<br /> <br /> <br /> Hunsaker, B.D., D.J. Steffen, CL. Topliff, C.L. Kelling, 2004. Characterization of protection in calves from systemic infection or disease by vaccination with modified-live noncytopathic bovine viral diarrhea virus type 1. Conference of Research Workers in Animal Disease.<br /> <br /> <br /> Klink,HA, R.P. Brady, C.L.Topliff, K.M.Eskridge, S. Srikumaran, C.L.Kelling. 2004. Influence of bovine respiratory syncytial virus F glycoprotein N-linked glycans on in vitro expression and on antibody responses in BALB/c mice. Conference of Research Workers in Animal Disease. <br /> <br /> <br /> Topliff, C.L., S.K.Chon, R.O. Donis, K.M. Eskridge, C.L Kelling. 2004. Translational efficiencies of the 5' untranslated region from eight genotype 2 bovine viral diarrhea virus field isolates varying in virulence. Conference of Research Workers in Animal Disease. <br /> <br /> <br /> <br /> Fulton, R.W., Burge, L.J., dOffay, J.M., Funk, R., Weaver, G.D., Van Campen, H., Johnson, B.J.: Immune Response Differences in Serums from Bovine Herpesvirus-1 Vaccinated Cattle: Depenndence of Viral Strarin. 47th Annual Meeting of AAVLD. October 22-24, 2004. Greensboro, NC.<br /> <br /> <br /> Fulton, R.W., Ridpath, J.F., Ores, S., Saliki, J.T., Burge, L.J., Confer, A.W.: Bovine Viral Diarrhea Virus (BVDV) Subtypes in Diagnostic Laboratory Accessions from Clinical and Necropsy Cases: Distribution of BVDV1a, BVDV1b, and BVDV2a Subtypes. 47th Annual Meeting of AAVLD. October 22-24, 2004. Greensboro, NC.<br /> <br /> <br /> Confer, A.W., Fulton, R.W., Step, D.L., Johnson, B.J., Ridpath, J.F.: Viral Antigen Distribution in the Respiratory Tract of Cattle Persistently Infected with Bovine Viral Diarrhea Virus Subtype 2a. 47th Annual Meeting of AAVLD. October 22-24, 2004. Greensboro, NC.<br /> <br /> <br /> Dabo SM, Anderson BE, Confer AW, Gupta S. Expression, Purification and Binding Activity of B. henselae Pap 31. Proceedings 105th Annual Meeting of American Society of Microbiology, Atlanta, GA. 2005<br /> <br /> <br /> Ayalew S, Blackwood ER, Confer AW. Sequence diversity of the immunogenic outer membrane lipoprotein PIpE from Mannheimia haemolytica serotypes 1,2 and 6. Proceedings 105th Annual Meeting of American Society of Microbiology, Atlanta, GA 2005.<br /> <br /> <br /> Chase CCL, DM Miskimins, T Graham, L Braun, P Steen and J Ridpath. Evidence of bovine viral diarrhea virus persistent infection in two white-tail deer in southeastern South Dakota. Proceedings of the 37th annual conference of American Association of Bovine Practitioners, Fort Worth, TX, September 23-25, 2004, p. 169.<br /> <br /> <br /> Fogarty-Fairbanks K, CL Rinehart, WC Ohnesorge, MM Loughin and CCL Chase. Fetal protection against BVDV type 1 or 2 heterologous challenge. Proceedings of the 37th annual conference of American Association of Bovine Practitioners, Fort Worth, TX, September 23-25, 2004, p.171.<br /> <br /> <br /> Fogarty-Fairbanks K, J Campbell and CCL Chase. Subcutaneous dose of infectious bovine rhinotracheitis virus provides early protection against an intranasal challenge. Proceedings of the 37th annual conference of American Association of Bovine Practitioners, Fort Worth, TX, September 23-25, 2004, p. 289.<br /> <br /> <br /> Tigabu B, CCL Chase, LJ Braun. BVDV influences the expression of Toll-like receptors. Abstract W13-4. 24th Annual Meeting of American Society for Virology, University Park, PA June 18-22, 2005.<br /> <br /> <br /> Donovan, DC, Barton, MH, Norton, N, Ely, LO, Hurley, DJ. Modulation of innate immunity by in vitro treatment of keukocytes with CD14, lactoferrin and IgG, (Abstract) pg 39 Proceedings of the 84th CRWAD meeting, Chicago, IL November 14-16, 2004<br /> <br /> <br /> Okinaga, T, Hurley, DJ, Woolums, AR, Miao, C, Zarlinga, DS. Comparison of bovine cytokine gene experession as measured by competitive and real-time PCR. (Abstract) pg 41 Proceedings of the 84th CRWAD meeting, Chicago, IL November 14-16, 2004<br /> <br /> <br /> Okinaga, T, Hines II, ME, Hurley, DJ. Real-time PCR measurements of cytokine mRNA from cattle and goats. ( Abstract) pg 40 Proceedings of the 84th CRWAD meeting, Chicago, IL November 14-16, 2004<br /> <br /> <br /> Reber, AJ, Okinaga, T, Tanner, M, Woolums, AR, Hurley, DJ. Development of immunity after vaccination with MLV or killed BVD vaccines. ( Abstract) pg 40 Proceedings of the 84th CRWAD meeting, Chicago, IL November 14-16, 2004<br /> <br /> <br /> M. Wiggins, A. Woolums, D. J. Hurley, D. Cole, S. Sanchez. The prevalence of Mycoplasma bovis in a subpopulation of Georgia cattle, (Abstract) Proceedings of the 84th CRWAD meeting, Chicago, IL November 14-16, 2004<br /> <br /> <br /> BOOK CHAPTER<br /> <br /> Vaccines, July 2005. Blackwell Publishing, Ames, IA.: Bovine Viral Diarrhea Virus: Diagnosis, Management and Control. Editors, Dr. S. Goyal and Dr. J. F. Ripdath. Pp. 209-222.<br />

Impact Statements

1. OBJECTIVE 1 (Impact of Findings): Data regarding the prevalence of Mycoplasma bovis in Georgia backgrounded/stocker cattle will provide producers, veterinarians, and researchers with previously unavailable information to assist their decision making regarding practices related to control of disease due to M. bovis. A rapid detection of BVDV in cell culture media using a biosensor has been demonstrated. Further development may make this a useful tool for the rapid and economical identification
2. OBJECTIVE 1 (Impact of Findings contd): Bronchopneumonia continues to be the major cause of feedlot morbidity. However the major pathogen associated with bronchopneumonia morbidity in Michigan appears to be Mycoplasma bovis. BVDV is often found in conjunction with M. bovis as well as other respiratory pathogens. PCR targeting Pm0762 and Pm1231 from Pasteurella multocida provides a useful means of rapidly and precisely identifying this species and differentiating it from other species.
3. OBJECTIVE 2 (Impact of Findings): Data from the study of the agreement between various assays of cell mediated immunity in calves vaccinated against BVD should improve the ability of researchers to make choices regarding which assays of cell mediated immunity are appropriate when they design research projects to characterize vaccines. Data indicating that changes in pH affect the function of leukocytes should provide impetus to manage cattle in ways that minimize the development of diseases (s
4. OBJECTIVE 2 (Impact of Findings contd): Studies on the lympho-suppressive activity of M. bovis and the interaction of the mycoplasma with endothelial cells provide basic knowledge for the description of virulence factors of the mycoplasma, and for understanding how lung lesions develop during respiratory infection and its systemic components. Toll like receptor 2 and 4 real time PCR assays was developed for molecular pathogenesis studies with BVDV and macrophages were conducted.
5. OBJECTIVE 2 (Impact of Findings contd): Studies have helped define the comparative pathogenesis of neurovirulent (BHV-5) and non-neurovirulent (BHV-1) bovine herpesviruses and the role of Us9 in anterograde neuronal transport. A clear understanding of the molecular interactions of the M. haemolytica leukotoxin at the cellular level could lead to new novel preventions and therapies for BRD.
6. OBJECTIVE 3 (Impact of Findings): Antimicrobial peptides such as cecropin B are useful in inhibiting M. haemolytica 1:A colonization. Sub-MICs of antibiotics effect protein expression in M. haemolytica, H. somnus, and P. multocida, including some proteins that could be important for virulence. These findings may elucidate the mechanism behind the beneficial effects of prophylactic antibiotic use in cattle.

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Report Information

Participants

*Woolums, Amelia (awoolums@vet.uga.edu)- U of Georgia;


*Czuprynski, Chuck (czuprync@svm.vetmed.wisc.edu)- U of Wisconsin;


*Fulton, Robert (Robert.Fulton@okstate.edu)- Oklahoma State U;


*Chowdhury, Shafiqul (chowdh@vet.k-state.edu)- Kansas State U;


* Chase, Chris (christopher_chase@sdstate.edu)- South Dakota State U;


*Ricardo Rosenbusch (rfrosenb@iastate.edu)- Iowa State U;


*Dan Grooms (groomsd@cvm.msu.edu)-Michigan State U;


*Sam Maheswaran Sam (mahes001@tc.umn.edu)-U. Minnessotta;


*Gary Sherman (gsherman@reeusda.gov)-USDA CSREES;


Mike Overton U of Georgia;


Dave McClenahan U of Wisconsin;


*Voting member

Brief Summary of Minutes

Stations reporting but not attending: Louisiana, Nebraska.


Adopted agenda:


SEPTEMBER 20:


8:00-8:30, registration;


8:30, welcome (Dr. Chowdury); welcome to Minnesota (Dr. Maheswaran).


8:45-10:30: Address and discussion with Dr. Bert Stromberg, Associate Dean for Research, University of Minnesota College of Veterinary Medicine.


10:30-10:50: Break. 10:50-12:00: Station reports.


12:00-1:00 PM: Lunch.


1:00-4:00: Station reports.


4:00-5:30: Address and discussion with Dr. Gary Sherman, USDA CSREES.


5:30: Adjourn



SEPTEMBER 21:


8:00-8:20: station reports.


8:20-9:00: Business Meeting.


9:00-10:30: Open forum with AABP attendees regarding needs in bovine respiratory research.


10:30-10:50: Further discussion of plans for national summit on future of BRD research.


10:50: Adjourn.



Key discussions:

Meeting with Dr. Stromberg, Associate Dean for Research, College of Veterinary Medicine, University of Minnesota: Dr. Stromberg presented an overview of research activities at the University of Minnesota College of Veterinary Medicine. As he is an Administrative Advisor for another CSREES Regional Project, he presented a short summary of the current status of the Regional Project Program: funding has been cut, but NC-107 was recognized to be a historically strong project and administrators were glad the project was renewed. Project members presented Dr. Stromberg with concerns regarding the loss of funds for the project, other research historically funded through Hatch money, and lack of funding for BRD research specifically and animal health research in general. Dr. Stromberg agreed with these concerns; noted that CSREES held a listening meeting in Kansas City in 2005, and there was some support from industry for BRD research. Dr. Stromberg pointed out that government research funding will always be directed at what producers and their interest groups consider most important. If we want more funding for BRD research, we need to get the cattle industry behind us.



After Dr. Stromberg left, the group continued to discuss the problem of lack of funding for BRD research and apparent decreased interest in participation in the regional project. Attendance has been relatively poor for the past two years, and it has become rare for voting members to bring guests (other researchers, graduate students) with them. The consensus of those attending this year was that the group needed to find ways to get more and more consistent funding for BRD research, which could then (we hope) improve the attendance at this meeting. If funding and attendance do not improve, it does not appear that the project will survive much longer. Discussion led to the idea that NC-1027 should host a national summit on the future of BRD research. We would invite representatives of state and national producer organizations (NCBA, national dairy heifer rearers association, others) as well as reps from USDA, and other relevant officials. The point of the summit would be to ask the industry whether they think BRD warrants ongoing research, and, if they do, to ask that they make coordinated efforts to get Congress, USDA, and others to improve research funding. If producer organizations are not willing to make this effort, the group agreed that this would be a signal that there was no real support by the cattle industry for BRD research, and the small amount of money available through the project would not warrant the effort required to keep NC-1027 going.



Other reasons for the national summit: solicit input from the cattle industry on what should be the focus of BRD research in coming years; discuss the problem of relative lack of funding for animal research as a whole (point was made that USDA research budget is reportedly about $1 billion, while NSF research budget is about $12 billion, and NIH is even morewhy the disparity when agriculture is a major portion of the U.S. economy?), and the problem of lack of young scientists going into animal health research. Point was raised that most people being hired into basic science departments at vet schools are not people with a primary research focus on animal disease, but rather people with research focus that enables them to compete for NIH R01 grants. Thus, as members of NC-1027 retire, it is expected that they will not be replaced by new people with a focus on BRD. Thus a serious threat to animal health research is attrition of scientists.



The meeting with Dr. Sherman on Wednesday afternoon also focused much on the problem of diminished funding available to members of NC-1027 for bovine respiratory disease research. Many project members get no support, or only travel support, for their involvement in NC-1027. It was noted that at some schools, Formula Funds are used to support start-up funds for faculty writing NIH grantspeople doing animal health research may get little or no support from Formula Funds; this depends on the discretion of their administrators. Dr. Sherman was attentive and sympathetic to these problems. He noted that in a climate in Washington D.C. where many budgets are being cut, animal health research is actually getting small increasesbut he agreed with the point that the problems NC-1027 members are experiencing are symptomatic of the larger problem of the relatively serious lack of funds for animal health research in general. He reminded us that he is in charge of Formula Funds, does not have influence at NRIbut he realized that lack of funds through both funding arms of USDA is a problem. He asked that NC-1027 draft a short letter outlining current problems with the funding for the regional research project, and he will try his best to use our input to improve the way funds are made available.


Open forum for AABP attendees was generally considered a success, although miscommunication with AABP organizers led to forum not being advertised widely. Only a small number of people attended (no more than 10 people outside the technical committee), and only 3 were producers, but those who attended contributed much useful input. Major points made by the producers who attended were that they perceived currently available vaccines and antibiotics to be relatively effective, but BRD is still a widespread problem, at least in part due to younger calves being brought into feedyards. Cheap corn allows feedlots to bring in more higher risk cattle than in past. Also had good discussion among rep from FDA, rep from biologicals industry, NC-1027 members, and producers on issues of concern to allrequirements for vaccine and antibiotic labelling, particularly.


Research needs identified by producers who attended: more research on ways to prevent disease at the level of the cow-calf producer (before animals leave for feedlot); more development of cow-side tests to identify BRD etiologies and biological markers that predict prognosis; and more research on causes and control of respiratory disease in nursing beef calves. Little discussion of BRD in dairy animals, probably only because no dairy producers attended. Detailed notes of discussion were taken by Dr. Woolums; contact her if you would like to review them.


Business meeting: Meeting opened by Chairman Dr. Chowdhury at 8:20 AM on Thursday September 21. Minutes of 2005 meeting approved. Discussion of who will serve as Chairman next year. Dr. Briggs from NADC was supposed to serve as Secretary this year but no one has heard from him. Group agreed that he should be called to see if he will be able to serve as Chair next year. If he cannot, Dr. Chris Chase has agreed to serve as Chair next year; if Dr. Briggs can serve as Chair, Dr. Chase will serve as Secretary. Discussion of plans for national summit (see above) began, but had to be cut short due to time (due to open forum scheduled at 9 AM). Business meeting was concluded at 9 AM, but further discussion of national summit occurred from 10:30-10:50 AM. It was agreed that the national summit should be held in 2007. Dr. Grooms and Chowdhury agreed to write a conference proposal to NRI for the November 2006 deadline to try to get funds for the conference. Pros and cons of having conference in conjunction with AABP (in Vancouver, Canada in 2007) were discussedconcluded that the national summit should be held at a time separate from AABP or other meetings to ensure that discussion is focused, and attendance not diluted by other distractions. Consensus: national summit will be held in Washington D.C. Representatives from national and state cattle associations, USDA, AAVMC, and other relevant and influential organizations will be invited; travel will be supported for individuals we wish to have speak (e.g., President of NCBA Gary Webber, who spoke in support of needs for BRD research at 2005 CSREES Listening Meeting). Drs. Chase and Woolums will plan agenda with input from committee and plan local arrangements. Tentative date: first week of October, 2007.


2007 NC-1027 Technical Committee meeting will be held in conjunction with the national summit. Consensus that meetings after 2007, if they occur, should be held in conjunction with AABP, but members would most likely not have time and money to travel both to the summit and also to a Technical Committee meeting in conjunction with AABP in one year.


Meeting of Technical Committee adjourned Sept. 21, 10:50 AM.


Assigned responsibilities/deadlines/target dates:
Dr. Woolums will record and distribute minutes of 2006 meeting.
Dr. Chowdhury will prepare annual report (due 90 days from the date of our meeting).
Dr. Woolums will draft a short letter to Dr. Gary Sherman, outlining current problems for the regional project, and will send to group for comment.
Dr. Grooms and Dr. Chowdhury will write USDA NRI conference grant to obtain support for national summit on future of BRD research; due November 29, 2006.
Dr. Woolums and Dr. Chase will prepare draft agenda and list of invitees for national summit and distribute to membership within the next 1-2 months. Dr. Woolums will identify and reserve an appropriate location for the summit in the Washington D.C. area within the next month.


Next meeting information: To be held in conjunction with an NC-1027 sponsored national summit on the future of BRD research in Washington D.C., first week of October 2007. More details to follow.





INTERSTATION COLLABORATION AND INTERACTIONS (2001-2006)


SD, NE, OK and AL collaborated on an issue of Veterinary Clinics of North America focused on bovine viral diarrhea virus


SD and MI collaborated with CA on a book titled 5-Minute Veterinarian


MI worked with SD, KS, OK, AL, OH and NADC in identifying cattle persistently infected with BVDV for natural fetal challenge study.


SD, GA, CA, and NE collaborated on BRSV challenge models


SD, AL, MI, and NADC shared various BVDV strains and collaborated on developing new challenge models.


SD and GA collaborated on bovine immunology studies.


SD shared BHV-1 strains with KS, U of Pennsylvania and Princeton.


NE, GA and CA collaborated on a vaccinology course for veterinarians and veterinary students.


OH worked with SD, KSU, CA, IA, WCVS and Pfizer in developing and teaching a graduate level course in vaccinology.


GA collaborated with University of Montreal and NIH on new vaccine vehicles and delivery systems.


GA collaborated with Merial in measuring vaccine efficacy across a multi assay platform.


KS and NE shared reagents related to BHV-1 and BHV-5 research.


CA shared BRSV isolates with SD and U of Tennessee.


NADC and OK in constructing and evaluating new mutant P. multocida vaccine.


NADC, OK and New Mexico State on evaluating mucosal immunity to oral M. haem/P. multi vaccine


NADC and MN collaborated on generating leukotoxin knock out mutants of M. haemolytica.


NADC, NE, OK, WI and MN share monoclonal antibodies directed against M. haemolytica leukotoxin.


OK and NADC collaborated on sequencing of multiple BVDV isolates.

Accomplishments

<br /> <br /> <br /> OBJECTIVE 1: IDENTIFY EMERGING AND RE-EMERGING AGENTS AND DEVELOP DIAGNOSTIC METHODS FOR BOVINE RESPIRATORY DISEASE (BRD).<br /> <br /> <br /> CALIFORNIA:<br /> <br /> <br /> Infection with Hemophilus somnus on day 6 of BRSV infection leads to a longer febrile period, persistent cough, and a more severe lesion at necropsy.<br /> <br /> <br /> GEORGIA:<br /> <br /> <br /> 1. In collaboration with IA, PCR and IFA assays are being developed to identify pathogenic bovine mycoplasmas. <br /> <br /> <br /> 2. The prevalence of Mycoplasma bovis in nasal swabs of cattle arriving at backgrounding/stocker operations in Georgia was evaluated. The herd level prevalence of M. bovis shedding was high (6 of 9 operations positive), but the animal-level prevalence was low, with 2% - 6% of animals shedding. At the individual level, agreement between culture of nasal swabs and direct PCR of nasal swabs was only moderate, while agreement at the farm level for identification of any animal shedding M. bovis was excellent. Calves shedding M. bovis were significantly more likely to have a fever (p < 0.01, odds ratio = 10.6) than calves not shedding M. bovis. <br /> <br /> <br /> IOWA:<br /> <br /> <br /> 1. Nasal sampling for Mycoplasma bovis was predictive of the biotypes of the mycoplasma in tracheal wash samplings from the same calf. Phenotyping of strains by antibiotic sensitivity was more discriminating than genomic fingerprinting.<br /> <br /> <br /> 2. VspA antigen of M. bovis was used as specific target for ELISA serology and immunohistochemistry (IHC). Data suggested that ELISA serology based on VspA may not be a sensitive indicator of exposure to M. bovis.<br /> <br /> <br /> 3. A whole cell ELISA was more sensitive than a peptide ELISA. Detection of M. bovis in the noses of calves was most sensitive when culture was followed by immunoblot. A generic mycoplasma PCR demonstrated that mycoplasmas other than M. bovis are common in most calves.<br /> <br /> <br /> KANSAS STATE:<br /> <br /> <br /> The relationship between BVDV biotype and genotype and characteristics of the resulting disease were examined for 117 isolates. Specific disease syndromes were not confined to specific virus biotypes or genotypes.<br /> <br /> <br /> LOUISIANA: <br /> <br /> <br /> Over 300 bovine coronavirus strains have been isolated from animals that experienced acute respiratory disease during two shipping fever epizootics. Comparing the sequences of the enteric and lung genomes has revealed numerous single nucleotide substitutions.<br /> <br /> <br /> MICHIGAN:<br /> <br /> <br /> 1. The usefulness if IHC for identifying neonatal calves persistently infected with BVDV was evaluated and determined to be very accurate.<br /> <br /> <br /> 2. A rapid detection of BVDV in cell culture media using a biosensor was demonstrated. Detection of cattle persistently infected with BVDV using ear notches was shown to be most consistent when compared to serum and nasal swabs. <br /> <br /> <br /> 3. Mycoplasma bovis is an emerging pathogen in feedlot calves and is believed to be responsible for an increasing incidence of nonresponsive chronic pneumonia, polyarthritis and mortality. <br /> <br /> <br /> MINNESOTA:<br /> <br /> <br /> The infectious agents associated with BRD were monitored by bacterial culture, virus isolation, viral serum neutralization tests, viral serum hemagglutination inhibition (HI) test,direct fluorescent antibody techniques (DFA), immunohistochemistry (IH), and PCR tests.<br /> <br /> <br /> MISSISSIPPI:<br /> <br /> <br /> 1. Persistent BVD virus infection was more prevalent in light weight placement cattle than in heavier weight placement cattle. Most positive cattle were identified as sick and pulled within the first 10 days on feed.<br /> <br /> <br /> 2. By comparing transcriptional regulator gene sequences from the P. multocida genome with other DNA sequences at GenBank, two genes (Pm0762 and Pm1231) were identified that are uniquely present in this species. <br /> <br /> <br /> <br /> NADC:<br /> <br /> <br /> 1. Characterization of goat adenovirus isolates from Minnesota and Canada indicate that there may be across-species antigenic relationships among the ruminant Mastadenovirus, although they differ at the genetic level. <br /> <br /> <br /> 2. Several widespread outbreaks of severe acute BVD could be traced to a single strain of BVDV. Unlike most BVDV strains, this strain spread quickly from herd to herd and caused significant death losses. To date, the only way to determine if a virus caused severe disease or caused mild disease was to infect animals. A research model was developed that uses cultured cells rather that animals to differentiate viral virulence. This model will reduce the need to use live animals and will significantly cut the cost and difficulty of studying BVDV virulence.<br /> <br /> <br /> OKLAHOMA:<br /> <br /> <br /> 1. Serum concentrations of four acute phase proteins were evaluated as either prognostic or diagnostic tools regarding the occurrence of bovine respiratory disease in marketing and shipping stressed feedlot cattle.<br /> <br /> <br /> 2. In collaboration with NADC, bovine viral diarrhea virus (BVDV) subtype 1b was shown to be transmitted by persistently infected calves to both vaccinated and non-vaccinated calves, including BVDV1b seropositive calves. <br /> <br /> <br /> 3. An antigen capture ELISA (AC ELISA) test kit and a RT-PCR test were used to detect bovine coronavirus (BCV) in nasal swabs collected from four groups of cattle. While the AC ELISA is a useful screening test because of ease of use, the RT-PCR test identified more BCV positive cattle.<br /> <br /> <br /> 4. We continue to monitor for BVDV persistently infected (PI) cattle in feedlots by testing all cattle dying via immunohistochemistry (IHC) of formalin fixed ear. Ear notches stored in 10% neutral buffered formalin remained BVDV IHC positive after extended storage: up to one year (one calf positive after 4 years). Since 2003 we have tested samples from five feedyards in Oklahoma, Colorado, and Kansas. There were 3463 samples tested with 116 positive (3.3%). The range of IHC positives in the five feedyards was 2.6% to 5.4%. The owners of the cattle are being contacted to determine vaccination histories. The pen data for morbidity, mortality, treatment costs, number of treatments, and cost of gain are being collected for analysis. <br /> <br /> <br /> 5. The prevalence of BVDV subgenotypes and biotypes was determined from 131 BVDV positive samples from a diagnostic laboratory. There were 131 BVDV samples represented by 117 noncytopathic (NCP), 11 cytopathic (CP) and 3 cases with mixed NCP and CP biotypes. The NCP isolates were more common (P<0.05) than the CP and NCP/CP combination. There were more BVDV1b subgenotypes 60/131 (45.8%) than BVDV1a, 37/131 (28.2%) or BVDV2a 34/131 (26.0%). Only one of the 131 viruses was genetically similar to the strains present in the U.S. vaccines. <br /> <br /> <br /> 6. Tests were compared to identify BVDV PI calves entering feedlots. The antigen capture ELISA (ACE) test on initial test was followed by IHC, viral isolation, and PCR of the serum of ACE test positive calves. Two of 88 ACE test positive calves were negative with the other tests, yielding 2 false positives. The PI rate was 0.4% (86/21,743).<br /> <br /> <br /> SOUTH DAKOTA:<br /> <br /> <br /> 1. Principal respiratory pathogens identified were similar to preceding years. Pasteurella multicida, Mannheimia haemolytica, and noncytopathic BVDV were most frequently isolated. An interesting finding was the increase in IBR abortions, apparently related to the use of MLV IBR-BVDV vaccines in pregnant animals.<br /> <br /> <br /> 2. Immunoperoxidase BVDV outgrowth test for the detection of BVDV PI animals was used on 7409 animals and there were 17 positives. Ear notch BVDV tests were conducted on 21,048 samples and there were 150 positives. PCR tests were done for BVDV and 316 tests (1547 samples) were tested and 39 positives were detected.<br /> <br /> <br /> WISCONSIN:<br /> <br /> <br /> The Wisconsin Veterinary Diagnostic Laboratory provided data regarding testing for, and diagnosis of, bovine viral pathogens during the year 2004. As in past years, the vast majority of tests requested are for detection of BVDV. The highest percentage of positive tests is for BRSV. <br /> <br /> <br /> OBJECTIVE 2: CHARACTERIZE MECHANISMS AND INTERVENTION TARGETS IN PATHOGENESIS OF BRD AT THE MOLECULAR, CELLULAR, AND HOST LEVEL.<br /> <br /> <br /> CALIFORNIA:<br /> <br /> <br /> We have shown that BRSV facilitates development of IgE antibodies to inhaled allergen. BRSV infected allergen (ovalbumin, OA) aerosol exposed calves had detectable OA specific IgE by day 10 and initial analysis of results show a correlation between IgE responsiveness and IL-4 producing T cells in lymph.. <br /> <br /> <br /> GEORGIA:<br /> <br /> <br /> 1. Messenger RNA for IL-4 and IFN-gamma was measured using RT-cPCR of RNA from lung and bronchoalveolar lavage fluid cells from calves challenged with BRSV. The results show that BRSV infection induces a T helper type 1 response.<br /> <br /> <br /> 2. The progression of immune activities following vaccination with modified live virus (MLV) or killed bovine viral diarrhea (BVD) virus was evaluated. Comparison of different tests of immune response showed poor agreement among tests commonly used to measure cellular or humoral immunity. <br /> <br /> <br /> 3. A survey of the relationship between management practices and risk of acute interstitial pneumonia (AIP) at U.S. feedlots was undertaken. The total number of cattle placed by respondents was 2,495,439; representing approximately 10% of the cattle placed in feedlots in 2000. Feedlots in northern states were less likely to report AIP as a cause of morbidity/mortality, while larger feedlots and feedlots placing higher proportions of yearlings more often recognized AIP. Although heifers were recognized to account for 62% of AIP deaths, feedlots placing a large proportion of heifers were not more likely to recognize AIP as a cause of morbidity/mortality than feedlots placing a small proportion of heifers. Feedlots that vaccinated over 95% of cattle for Mannheimia/Pasteurella were less likely to recognize AIP as a cause of morbidity/mortality.<br /> <br /> <br /> 4. Studies undertaken with Iowa confirmed that field isolates of Mycoplasma bovis have more pronounced effect to impair bovine neutrophil function than high pass laboratory isolates, indicating that M. bovis likely causes disease in part through impairing neutrophils function.<br /> <br /> <br /> 5. The impact of whole, live maternal cells, freeze lysed maternal cells, and cell free colostrum on the phenotypic and functional development of innate and adaptive immune function in calves from birth to 6 weeks of age was studied. Colostrum containing whole live cells improved innate and adaptive immune function in calves. <br /> <br /> <br /> IOWA:<br /> <br /> <br /> 1. A lymphotoxic activity is described for Mycoplasma bovis, and this virulence factor was not observed in other species of bovine mycoplasmas.<br /> <br /> <br /> 2. Primary cell cultures of bovine lung alveolar type 2 cells were developed. These will be very valuable for the study of bovine lung pathogens. <br /> <br /> <br /> 3. Aortic endothelial cell cultures were infected with an abscessing or a non-abscessing strain of Mycoplasma bovis. Cells were examined for ICAM-1 up-regulation, nitric oxide synthase activation, and VCAM-1 up-regulation. Only VCAM-1 expression was upregulated. <br /> <br /> <br /> 4. A lymphocyte-suppressive activity of Mycoplasma bovis was found to reside in a peptide cleaved off a surface-exposed membrane protein of the organism. The native, or recombinant form of this peptide had suppressive activity. The immunosuppressive peptide was expressed on nearly all colonies from most strains of M. bovis. <br /> <br /> <br /> KANSAS:<br /> <br /> <br /> 1. The role of envelope proteins gE and US9 in the anterograde transport of BHV-1 following reactivation in TG neurons of calves was investigated. The data suggest that in the absence of Us9 or gE, the latent virus can reactivate in the TG, however the viral anterograde axonal transport in nasal and ocular epithelium is defective. During primary infection, calves infected with BHV-1 wild type, gE deleted, or US9 deleted recombinant viruses shed similar amounts of virus from the eye and nasal cavity. When reactivation form latency was initiated with dexamethasone, virus shedding was observed only in calves infected with wild type virus, but not in gE and US9-deleted BHV-1 viruses. We suggest that the gE and US9 play a role in anterograde transport from TG neurons back to the nasal epithelium, cornea and conjunctiva.<br /> <br /> <br /> 2. The genome of BHV-1 has been cloned as a bacterial artificial chromosome (BAC). Using a two step Red recombinase system a BHV-1 BAC mutant has been constructed in which the cytoplasmic tail of the gE gene has been truncated. The data show that gE cytoplasmic domain is required for posttranslational modification of the gE. <br /> <br /> <br /> 3. Bovine alveolar macrophage neurokinin-1 (NK-1) and the in vitro response of alveolar macrophages to Substance P (SP) exposure were investigated. The results suggest that bovine alveolar macrophages respond to SP at least in part by enhancing phagocytosis and TNF production. <br /> <br /> <br /> LOUISIANA:<br /> <br /> <br /> The spike glycoproteins encoded by two prototypic respiratory and enteric bovine coronaviruses were codon optimized. This codon optimization resulted in high gene expression in transient assays unlike the wild type genes that failed to significantly express in transient expression systems.<br /> <br /> <br /> MICHIGAN:<br /> <br /> <br /> Research determined that administration of a vaccine for leptospirosis in cattle (Spirovac") had no effect on the response of cattle in the CFT or INF³ tests for bovine tuberculosis.<br /> <br /> <br /> MINNESOTA:<br /> <br /> <br /> 1. Studies examined the role of the major ligand-binding domain in LFA-1 in both binding to M. haemolytica LktA and mediating LktA-induced effects. The results demonstrated that the LktA binding domain is within the CD18 molecule, and that binding site lies within the EGF-3 domain of CD18 which encompasses amino acids 541 to 581. However, cellular activation upon LktA binding requires the interaction of CD18 and CD11a. Recently, this group has successfully cloned and sequenced the bovine CD11a coding sequence which has 81.6% nucleotide identity to human CD11a.<br /> <br /> <br /> 2. We mapped the site within the bovine CD18 that is required for LktA binding and its biological effects. To accomplish this, we created several bovine (B) x human (H) chimeric CD18 constructs by domain swapping replacing the nucleotide sequences in the cDNA encoding the amino acids in the extracellular portion of human CD18 with corresponding sequences from the bovine CD18. binding site<br /> <br /> <br /> 3. Expression of the reputed M. haemolytica leukotoxin receptor, bovine LFA-1, in the human erythroleukemic K562 cell line was successfully accomplished. The expressed product was also found to be functionally active. <br /> <br /> <br /> MISSISSIPPI:<br /> <br /> <br /> 1. DNA adenine methylation in P. multocida and M. haemolytica have been demonstrated; data indicated that appropriate expression of Dam is required for virulence of P. multocida.<br /> <br /> <br /> 2. Prophylactic use of feed additive antibiotics in cattle significantly reduces respiratory morbidity/mortality, but the basis for benefit is not known. We compared the proteome of respiratory pathogen M. haemolytica from cultures grown in the presence of ¼ MIC of both antibiotic preparations to that obtained without the antibiotic treatment. Expression of 85 proteins was significantly altered by at least one of the antibiotic treatments. The most notable sub-MIC effect was a significant decrease in the expression of leukotoxin A. <br /> <br /> <br /> 3. We identified mannose receptor (MR) as important in endocytosis in bovine monocytes. We have also demonstrated that antigen uptake through MR-mediated endocytosis, an important APC function, is affected in monocytes in the early stage of BVDV infection, with both BVDV biotypes. We identified the following proteins related to antigen uptake: the galactose binding lectin, MyD-1, clathrin light chain A and MR precursor. We also identified 8 proteins related to cytoskeleton such as actin, beta actin and gamma actin. <br /> <br /> <br /> <br /> MISSOURI:<br /> <br /> <br /> Studies determined the expression of gelatinases in healthy calf lungs by examining MMP activity in bronchoalveolar lavage fluid from calves reared in the clinic. All calves possessed gelatinase activity as MMP 2 and MMP 9. <br /> <br /> <br /> NADC:<br /> <br /> <br /> 1. An immunoglobulin-binding protein was demonstrated in whole cell sonicate and culture supernatant preparations from an M. haemolytica serotype 1.<br /> <br /> <br /> 2. Serial analysis of gene expression (SAGE) was used to identify differential gene expression in cultured epithelial and lymphatic cells following infection with BVDV. Findings indicated increased protein translational potential, increased nascent peptide transport and enhanced intracellular membrane targeting and transport.<br /> <br /> <br /> 3. A method for isolation of respiratory tract dendritic cells from lung tissue of neonatal lambs as well as adult sheep was developed. This is the first documented isolation of dendritic cells from neonates, and shows that they are similar to adults phenotypically and functionally. This is in contrast to the current dogma. <br /> <br /> <br /> NEBRASKA:<br /> <br /> <br /> 1. Subpopulations of lymphocytes were more markedly altered in peripheral blood and lymphoid tissues from co infected calves compared to calves infected with either BRSV or BVDV alone. Extensive apoptosis of dendritic cells and lymphocytes occurred in the cortex of mesenteric lymph nodes of calves infected with BVDV.<br /> <br /> <br /> 2. We demonstrated that heat shock protein gp96 peptide complexes isolated from a murine cell line transduced with glycoprotein D (gD) of BHV 1 induce CTLs specific for BHV 1 in mice. Calves infected with the LR mutant exhibited mild clinical symptoms, but they sero converted.<br /> <br /> <br /> 3. Using a vaccinia virus T7-promoter expression system, expression of the single and combination N-glycosylation deletion F proteins of BRSV was characterized in COS-7 cells. <br /> <br /> <br /> 4. Translation efficiencies of the 5' untranslated region from BVDV type 2 isolates was evaluated using bicistronic reporter assays. Low virulence isolates translated with greater efficiency than high virulence isolates in rabbit reticulocyte lysates, We have now determined that in BT and BL-3 cells, the Npro coding region either had no influence or caused a significant decrease in IRES-mediated translational efficiency, with the exception of BVDV 890, where Npro increased IRES-mediated translational efficiency in BL-3 cells. Mutagenesis of IRES base 219 and/or 278 ameliorated suppression of the translational efficiency modulated by the Npro coding region. Results suggest interactions between the Npro coding region and nucleotides within and external to the IRES element influence translational efficiency. IRES element mutagenesis or addition of the Npro coding region to the 5 UTR enhanced the characteristic low translational efficiency of the high virulent isolate 890, while decreasing the translational efficiency of low virulent isolates, such as 7937. These results underscore the complex interplay of cellular factors influencing IRES-mediated translation. <br /> <br /> <br /> 5. Protection against systemic replication of BVDV type 1 in calves vaccinated with with a modified-live noncytopathic BVDV1 vaccine was evaluated. Post-challenge with NY-1, vaccinated calves were protected against systemic replication of challenge virus since they did not develop reduced leukocyte counts and were protected against viremia and infection of target lymphoid cells. <br /> <br /> <br /> 6. Several studies were undertaken to determine the mechanism by which BHV-1 establishes latency. <br /> <br /> <br /> a. A novel BHV-1 gene that is expressed in trigeminal ganglia of latently infected calves (ORF-E) was discovered. The BHV-1 LR gene encodes multiple functions that together regulate latency. The dominant function is performed by a protein encoded by ORF-2 that is absolutely required for the latency-reactivation cycle in cattle. The LR gene interferes with apoptosis, which promotes neuronal survival during the transition from acute infection to latency. The LR gene also appears to encode a small non-protein coding RNA that inhibits cell cycle progression. Finally, LR-RNA sequences or a small open reading frame appears to inhibit bICP0 expression (the gene that is anti-sense to the LR gene), and consequently can inhibit viral gene expression. <br /> <br /> <br /> b. bICP0 is considered to be most important transcriptional regulatory gene of BHV-1 and is antisense to the LR gene. In addition to regulating transcription, bICP0 is toxic to cells, but does not appear to directly induce apoptosis. bICP0 contains a C3HC4 zinc ring finger at its amino terminus. Since bICP0 does not specifically bind DNA, we have hypothesized that bICP0 interacts with transcription factors. Earlier studies demonstrated that bICP0 interacts with histone deacetylase 1 (HDAC1). HDAC1 represses transcription because it removes acetyl groups from histones, thus making chromatin transcriptionally inactive. We have also determined that bICP0 binds p300, a histone acetyltransferase that regulates transcription. We believe that the ability of bICP0 to interact with HDAC1 and p300 promotes productive infection. <br /> <br /> <br /> OKLAHOMA:<br /> <br /> <br /> 1. Three outer membrane proteins (OMPs) including a 95 kDa OMP from a bovine P. multocida grown in iron-depleted conditions were described.<br /> <br /> 2. Isolated bovine neutrophils were used to study the relationship between the duration and magnitude of the M. haemolytica leukotoxin-induced increase in intracellular calcium concentration and leukotriene B4 synthesis. High and sustained intracellular calcium concentration was necessary to stimulate production of leukotriene B4, which may play an important role in the pathogenesis of M. haemolytica infection. The gene for M. haemolytica outer membrane protein PlpE was cloned and expressed. Vaccination of cattle with rPlpE enhanced resistance against experimental challenge.<br /> <br /> <br /> 3. Calves given modified live virus (MLV) BVDV1a and 2a vaccine were protected against challenge using PI calves. Also antigen detection by the ACE test in fresh notches and IHC in formalin notches were negative in acutely infected calves.<br /> <br /> <br /> <br /> SOUTH DAKOTA:<br /> <br /> <br /> 1. BVDV infected macrophages down regulated MHC Class I and II and CD 14 surface markers. This down regulation correlated with the in vivo pathogenicity of the isolates with persistent infection strains down regulating MHC Class I and the acute disease strains down regulating MHC Class II and CD 14. IFN-alpha inhibited BVDV replication and RNA synthesis and its effect was dose, time and biotype dependent. CP/BVDV induced apoptosis as early as 24 hours post infection; p53 and caspase pathways were involved in the BVDV apoptosis.<br /> <br /> <br /> 2. BVDV strains that cause acute disease produce a soluble factor that down regulates un-infected macrophage functions and surface marker expression and nitric oxide (NO) production. <br /> <br /> <br /> 3. Depolymerization of the cytoskeleton (microtubules or actin) had a major effect on BHV-1 replication. We investigated the effect of wild-type (WT) or mutant strains on the integrity of cytoskeleton components, actin filaments, microtubules and intermediate filaments during the course of viral infection.<br /> <br /> <br /> 4. An RT-PCR test for the detection of Toll-like receptors 2 and 4 was developed. Monocyte-derived macrophages (MDM) were infected with BVDV strains of different virulence. The effect of BVDV strains on the mRNA expression level of MDMs of TLR-2 and -4 was evaluated. A BVDV strain from persistent infection significantly decreased the amount of mRNA of MDMs TLR-2 as compared to the mock and other strains. However, this virus has only minimal effect on TLR-4 mRNA expression. Thus, BVDV may modify the innate immune recognition by influencing the expression of toll-like receptors.<br /> <br /> <br /> 5. Forty-four calves were identified as BVDV positive and the strain was BVDV type 2a. Thirty-nine calves were transported to a university facility in September 2004; 36 were PI. These animals were analyzed over a 10-month period. The 5 UTR and E2 region of isolates were analyzed. The results indicate that the 5UTR was similar among all calves but one group of 7 calves had conserved changes in the E2 region. Twenty-four of the calves succumbed to mucosal disease during the experiment and CP-BVDV virus was isolated from 18 calves. The CP-BVDV is currently being sequenced to determine mutation differences. These results indicate that within a population of PI infected animals that the amount of genetic variation in the 5UTR and E2 that occurs over time is well conserved and that small variations in E2 region can occur within the same cohort but these changes occur very early in the infection. <br /> <br /> <br /> 6. The infectivity of BVDV white deer isolates in white tailed deer was evaluated. Eight white tailed deer fawns 4-6 weeks in age were placed in 2 groups: group 1 was inoculated with non-cytopathic (NCP) BVDV type 1b and group 2 was inoculated with NCP-BVDV type 2. A control group of two animals was also used. The results showed that white tail deer are susceptible to BVDV infection from white tail deer isolates. It remains to be determined if deer can transmit the virus to cattle or if deer can become persistently infected as calves.<br /> <br /> <br /> 7. Measurements of serum levels for 4 cytokines (TNF-alpha, IL-10, IL-1B and gamma interferon) were done in BVDV PI and control animals. Basal cytokine levels were similar between controls and PI animals. However TNF-alpha levels were elevated 10X in a calf 3 days prior to death. These same animals were analyzed over a 3 month period for the immunological changes. The most interesting finding was a 50% increase in B cells.<br /> <br /> <br /> TEXAS:<br /> <br /> <br /> There was no association of the specific polymorphisms in the AMPK gene family of the bovine and the incidence of BRD.<br /> <br /> <br /> <br /> WISCONSIN:<br /> <br /> <br /> 1. We continued investigations of the effects of M. haemolytica leukotoxin, cytokines, and BHV-1 on bovine leukocytes. Interaction of the leukotoxin (LKT) with LFA-1 was shown to be necessary for the previously described ability of cytokines to enhance LKT cytotoxicity. In collaboration with Minnesota, it was shown that preincubation of bovine PMNs with LKT or LPS enhanced cytotoxic activity of LKT. <br /> <br /> <br /> 2. M. haemolytica leukotoxin (LKT) was internalized by BL-3 cells and transported to the mitochondria, where it caused an increase in mitochondrial permeability. This process was dependent on LKT transport by lipid rafts and dynamin-2. <br /> <br /> <br /> 3. Studies of the molecular pathogenesis of Haemophilus somnus continued:<br /> <br /> a. H. somnus LOS caused activation of bovine platelets and upregulation of surface molecules that may contribute to the development of vasculitis and thrombosis seen in H. somnus infection. H. somnus and its LOS, as well as H. somnus activated platelets, can up-regulate expression of tissue factor and ICAM-1 (CD54), and down regulate thrombomodulin on bovine pulmonary artery and brain microvascular endothelial cells. We are currently evaluating whether these data reflect the release of PAF by bovine platelets in response to LOS, or suggest a role of the PAF receptor in binding to H. somnus LOS (as has been reported for the LOS of the human pathogen Haemophilus influenzae). <br /> <br /> <br /> b. Using primary cell culture and H. somnus, we have developed an in vitro model to study the sequence of events and mediators involved in the dysfunction of the blood brain barrier in bacterial infection. We have investigated the ability of H. somnus to attach to and invade primary cerebral microvascular endothelial cells (CMVECs). Attachment occurs in a dose dependent manner, but invasion is a rare event. <br /> <br /> <br /> 4. Studies of the VP22 of bovine herepesvirus-1 (BHV-1), a tegument protein that accumulates in the nucleus, indicate a possible regulatory function of VP22 within the nucleus, but how VP22 enters the nucleus is unknown. Despite the abundance of basic residues within this protein, no classic nuclear localization signal (NLS) motif has been identified. A mitochondrial targeting sequence in the C terminal 49 amino acids was identified, which overlaps with the sequence required for nuclear targeting. <br /> <br /> <br /> 5. Studies of intracellular pathways associated with leukocyte death following exposure to M. haemolytica LKT showed that LKT activates caspase-9 more than caspase-8, suggesting involvement of the mitochondrial pathway of apoptosis. The anti-apoptotic protein Bcl-2 decreased, while the pro-apoptotic proteins Bax and Bad increased. Phosphorylation of Akt-1, a signaling protein downstream of LFA-1 that usually leads to cell survival, was decreased following LKT exposure. <br /> <br /> <br /> OBJECTIVE 3: DEVELOP INTERVENTION STRATEGIES FOR CRITICAL CONTROL POINTS TO REDUCE THE IMPACT OF BRD.<br /> <br /> <br /> ALABAMA:<br /> <br /> <br /> Identified 6 potential antiviral compounds. Demonstrated that cattle persistently infected with BVDV negatively impact feedlot cattle<br /> <br /> <br /> CALIFORNIA:<br /> <br /> <br /> Research showed that a cDNA vaccine containing the BRSV N protein provided some degree of protection, and appeared to induce the greatest proliferation of peripheral blood lymphocytes after vaccination and during infection. <br /> <br /> <br /> GEORGIA:<br /> <br /> <br /> 1. Cytokine expression in calves vaccinated intranasally with modified live BRSV prior to virulent BRSV challenge was studied. Results showed evidence of both T helper type 1 (TH1) and T helper type 2 (TH2) cytokine production in vaccinated calves, in contrast to results in nonvaccinated calves, where TH1 responses predominated. <br /> <br /> <br /> 2. Acidic pH below 7.0 altered significantly the capacity of neutrophils to produce oxygen radicals and increased the level of neutrophil apoptosis in cattle.<br /> <br /> <br /> IOWA:<br /> <br /> <br /> 1. Calves infected intratracheally with Mycoplasma bovis responded with a Th2-like response characterized by IL-4 production by PBMCs and antigen-specific IgG1 serum antibody response; this may enhance disease due to slow clearance of the organism. In vitro activation of bovine gamma-delta-T cells was observed to occur when stimulated with M. bovis antigen, indicating activation of innate immunity. <br /> <br /> <br /> 2. Antimicrobial susceptibility of 223 recently recovered isolates of M. bovis was completed. There were no significant differences in susceptibility patterns that could correlate to geographical origin or type of disease presentation. Enrofloxacin, florfenicol, and spectinomycin were active. Oxytetracycline and chlortetracycline were active against half of the isolates, and very few were susceptible to tilmicosin. None were susceptible to erythromycin, ampicillin, or ceftiofur.<br /> <br /> <br /> KANSAS:<br /> <br /> <br /> 1. Near infrared spectroscopy (NIRS) was evaluated in a feedlot study as a means of noninvasively determining oxygen saturation StO2 of hemoglobin to identify animals as having undifferentiated bovine respiratory disease (UBRD).<br /> <br /> <br /> 2. Needle-free and conventional needle-andsyringe injection techniques were evaluated in two different studies of dairy calves and feedlot steers. Blood samples were collected from all animals at the time of vaccination and 21 days later, and the serum analyzed for antibody titers. On day 21 the serological response of heifers to the IBR fraction of the 5-way viral vaccine, MH bacterin and LP fraction of the 5-way Leptospira bacterin were not significantly different between routes of administration. On day 21 the serological response of steers to the IBR fraction of the 5-way viral vaccine and MH bacterin was significantly higher for the needle-free route of administration, while the serological response to the LP fraction was not significantly different between routes of administration. <br /> <br /> <br /> LOUISIANA:<br /> <br /> <br /> 1. Transfecting the upper respiratory tract of cattle with a gene coding for cecropin B does not result in a change in the indigenous and transient nasal flora. Results indicate that transfecting the upper respiratory tract with 100 ¼g of DNA per nostril inhibits colonization of a virulent strain of M. haemolytica 1:A. <br /> <br /> <br /> 2. The spike glycoproteins encoded by two prototypic respiratory and enteric bovine coronaviruses were codon optimized. <br /> <br /> <br /> MICHIGAN:<br /> <br /> <br /> In collaboration with AL, a study was undertaken to determine the effect that the continuous presence of PI cattle has on the overall performance of non-PI feedlot cattle, which shoed that BVDV PI cattle impact the performance of cohort feedlot cattle by increasing morbidity and decreasing average daily gain.<br /> <br /> <br /> NADC: <br /> <br /> <br /> 1. In collaboration with OK, a field trial was conducted on fall-shipped beef calves to evaluate a single-dose combination M. haemolytica/P. multocida edible modified-live vaccine formulation. Vaccination with a modified-live M. haemolytica/P. multocida product single-dose product top-dressed on feed improved weight-gain of calves over a 35 day feeding trial by 6.1 kg compared to unvaccinated ones.<br /> <br /> <br /> 2. New leukotoxin mutants of M. haemolytica serotypes 1 and 6 were constructed which express and transport the C-terminal approximately 1/3 of the leukotoxin structural gene. Mutants may be useful for vaccination of ruminant species. <br /> <br /> <br /> 3. Adenovirus appears to play a role the pathogenesis of outbreaks of respiratory disease in domestic and wild ruminants just as do the better known respiratory viruses. Virus infection may influence the function of pulmonary dendritic cells and thereby cause immunosuppression. <br /> <br /> <br /> OKLAHOMA:<br /> <br /> <br /> 1. Herds with a low morbidity rate had higher levels of BVDV1a antibodies than herds with a high morbidity rate. Calves with low levels of antibody to BVDV1a, P. multocida, and BVDV2 and BVDV2 had increased total treatment costs and decreased net value to owner.<br /> <br /> <br /> 2. The passive immunity transferred to calves from their dams was investigated in a beef herd. Health status at entry to a feedlot was evaluated in reference to performance and carcass value. There were increased numbers of treatments for the individual animals in calves with low antibody levels of M. haemolytica, BVDV1, BVDV2 and PI-3V. <br /> <br /> <br /> 3. During 2003 and 2004 there were reports of bovine herpesvirus-1 (BHV-1) disease in cattle with prior vaccination (often multiple doses) with modified live virus (MLV) vaccines. The disease was not associated with use of any one commercial vaccine. These 2003-2004 episodes had greater morbidity/mortality than expected. Serums were tested for BHV-1 antibodies in a 24-well plaque reduction assay using different BHV-1 strains. It appears that most of the vaccines induced serum antibodies that poorly neutralized the BHV-1 Cooper challenge strain and the field strain. High passages in cell culture may result in changes in virus neutralization properties of the BHV-1. The implications for differences in efficacy of the vaccines against field strains are unclear. Additional testing is in progress to detect genomic differences among the BHV-1 strains.<br /> <br /> <br /> <br /> SOUTH DAKOTA:<br /> <br /> <br /> 1. Isoflavones fed to cattle had a small effect on bovine herpesvirus 1 and no effect on NCP-BVDV type 1.<br /> <br /> <br /> 2. A study was done to compare the effect of two dairy cow vaccination programs with either an inactivated vaccine in the dry period vs. MLV in the fresh period. There was no difference in production parameters with the exception of somatic cell count that was higher in MLV animals. <br /> <br /> <br /> 3. Commercial modified live BHV-1 vaccine protected calves from challenge when administered 48, 72, and 96 hours (hr) prior to challenge. <br /> <br /> <br /> TEXAS:<br /> <br /> <br /> 1. Dual prophylaxis reduces the incidence and severity of BRD as compared to metaphylaxis alone.<br /> <br /> <br /> 2. Serum total antioxidant capacity (TACA) and serum malondialdehydes (MDA) were measured in transported cattle. Transportation stress decreased serum TACA and increased serum MDA. <br /> <br /> <br /> <br /> WISCONSIN:<br /> <br /> <br /> Research evaluated relationships between air quality, environmental risk factors, and calf respiratory health in 13 naturally ventilated calf barns. Factors that were significantly associated with a reduced prevalence of respiratory disease were reduced pen log10 cfu/m3 on BAP, presence of a solid barrier between each calf were significantly different pen, and increasing nesting score. <br /> <br />

Publications

PEER REVIEWED PUBLICATIONS (2001)<br /> <br /> <br /> Brock KV, Cortese VS. 2001. Experimental fetal challenge using type II bovine diarrhea virus in cattle vaccinated with a modified-live virus vaccine. Vet therapeutics. 2:354-360.<br /> <br /> <br /> Butler JA, Pinnow CC, Thomson JU, Levisohn S, Rosenbusch RF. 2001. Use of arbitrarily primed polymerase chain reaction to investigate Mycoplasma bovis outbreaks. Vet. Microbiol. 78: 175-181.<br /> <br /> <br /> Chouljenko VN, Lin XQ, Storz J, Kousoulas KG. 2001. Elucidation of the genomic nucleotide sequence of bovine coronavirus and analysis of cryptic leader mRNA fusion sites. Adv. Exp. Med. Biol. 2002. 494: 49-55.<br /> <br /> <br /> Chouljenko VN, Lin XQ, Storz J, Kousoulas KG, Gorbalenya AE. 2001. Comparsion of genomic and predicted amino acid sequences of respiratory and enteric bovine coronaviruses isolated from the same animal with fatal shipping pneumonia. J. Gen. Virol. 82: 2927-2933.<br /> <br /> <br /> Confer AW, Suckow MA, Montelongo M, Dabo SM, Miloscio LJ, Gillespie AJ, Meredith GL. 2001. Intranasal vaccination of rabbits with Pasteurella multocida A:3 outer membranes expressing iron-regulated proteins. Amer. J. Vet. Res. 62: 697-703.<br /> <br /> <br /> Confer AW, Montelongo M, Brown MJ, Fergen BJ, Clement JC. 2001. Onset of Serum Antibodies to Pasteurella (Mannheimia) haemolytica following vaccination with five commercial vaccines. Bov. Practitioner. 35: 141-148.<br /> <br /> <br /> DeBey BM, Lehmkuhl HD, Chard Bergstrom C, Hobbs LA. 2001. Ovine adenovirus serotype 7 associated mortality in lambs in the US. Vet. Pathol. 38: 644 648.<br /> <br /> <br /> <br /> <br /> Frazier M, Pence M, Mauel MJ, Ligget A, Hines ME, Sangster L, Lehmkuhl HD, Miller D, Styer E, West J, Baldwin CA. 2001. Endometritis in postparturient cattle associated with bovine herpesvirus 4 infection: 15 cases. J. Diagnos. Invest. 13: 502 508.<br /> <br /> <br /> Givens MD, Galik PK, Riddell KP, Stringfellow DA, Brock KV, Bishop MD, Eilertsen KJ, Loskutoff NM. 2001. Validation of a reverse transcription nested polymerase chain reaction (RTnPCR) to detect bovine virus diarrhea virus (BVDV) associated with in vitro-derived bovine embryos and co-cultured cells. Theriogenology. 56: 787-799.<br /> <br /> <br /> Grooms DL, Kaiser L, Walz PH, Baker JC. 2001. Study of cattle persistently infected with bovine viral diarrhea virus that lack detectable virus in their serum. J. Am. Vet. Med. Assoc. 219: 629-631.<br /> <br /> <br /> Hart ML, Mosier DA, Chapes SK. 2001. The response of Tlr-4-receptor positive cells to infection. 35th Annu. Soc. for Leuk. Biol., Honolulu, HI, J. Leukocyte Biol. supp. 67.<br /> <br /> <br /> Inman M, Zhange Y, Geiser V, Jones C. 2001. The zinc ring finger of bovine herpes virus 1 encoded bICP0 is necessary for transcriptional regulation and infection. J. Gen. Virol. 82: 483-492. <br /> <br /> <br /> Inman M, Lovato L, Doster A, Jones C. 2001. A mutation in the latency related gene of bovine herpesvirus 1 leads to impaired ocular shedding in acutely infected calves. J. Virol. 75: 8507-8515.<br /> <br /> <br /> Jeyaseelan, S, Kannan MS, Briggs RE, Thumbikat P, Maheswaran SK. 2001. Mannheimia haemolytica leukotoxin activates a non-receptor tyrosine kinase-signaling cascade in bovine leukocytes which induces biological activity. Infect. Immun. 69: 6131-6139.<br /> <br /> <br /> Jeyaseelan S, Kannan MS, Hsuan SL, Singh AK, Walseth TF, Maheswaran SK. 2001. Pasterella haemolytica leukotoxin  induced cytolysis of bovine leukocytes: Role of arachidonic acid and its regulation. Microb. Pathog. 30: 59-69. <br /> <br /> <br /> Kalfa VC, Jia HP, Kunkle RA, McCray Jr. PB, Tack BF, Brogden KA. 2001. Congeners of SMAP29 kill ovine pathogens and induce ultrastructural damage in bacterial cells. Antimicrob. Agents Chemother. 45: 3256-3261.<br /> <br /> <br /> Lafleur RL, Malazdrewich C, Jeyaseelan S, Bleifield E, Abrahamsen MS, Maheswaran SK. 2001. Lipopolysaccharide enhances cytotolysis and inflammatory cytokine induction in bovine alveolar macrophages exposed to Pasteurella (Mannheimia) haemolytica leukotoxin. Microb. Pathog. 30: 347-357.<br /> <br /> <br /> Leite F, Sylte M, OBrien S, Schultz R, Peek S, Van Reeth K, Czuprynski C. 2001. Effect of experimental infection of cattle with bovine herpesvirus-1 on the ex vivo interaction of bovine leukocytes with Mannheimia haemolytica leukotoxin. Vet. Immunol. Immunopathol. 84: 97-110.<br /> <br /> <br /> Malazdrewich C, Ames TR, Abrahamsen MS, Maheswaran SK. 2001. Pulmonary expression of tumor necrosis factor  alpha, interleukin  beta, and interleukin  8 in the acute phase of bovine pneumonic pasteurellosis. Vet. Pathol. 38: 297-310.<br /> <br /> <br /> Ramirez-Romero R, Brogden KA, Gallup JM, Sonea IM, Ackermann, MR. 2001. Mast cell density and substance P-like immunoreactivity during the initiation and progression of lung lesions in ovine Mannheimia (Pasteurella) haemolytica pneumonia. Microb. Pathogen. 30: 325-335.<br /> <br /> <br /> Walz PH, Bell TH, Wells J, Grooms DL, Kaiser L, Maes RK, Baker JC. 2001. Relationship between level of viremia and disease manifestations in calves experimentally infected with bovine viral diarrhea virus. Am. J. Vet. Res. 62: 1095-1103.<br /> <br /> <br /> Walz PH, Bell TH, Wells J, Grooms DL, Kaiser L, Maes RK, Baker JC. 2001. Platelet aggregation responses and virus isolation from platelets in calves experimentally infected with type I or type II bovine viral diarrhea virus. Can. J. Vet. Res. 65:241-247.<br /> <br /> <br /> Wang P, Hurley DJ, Braun LJ, Chase CCL. 2001. Detection of bovine herpesvirus 1 in peripheral blood mononuclear cells 8 months post infection. J. Vet. Diag. Invest. 13: 424-427.<br /> <br /> <br /> Wittum TE, Groteueschen DM, Brock KV, Kvasnicka WG, Floyd JG, Kelling CL, Odde KG. 2001. Persistent bovine viral diarrhea virus infection in U.S. beef herds. Vet. Prev. Med. 49: 83-94.<br /> <br /> <br /> Zhang Y, Jones C. 2001. The bovine herpes virus 1 immediate early protein (bICP0) is associated with histone deaetylase 1 to activate transcription. J. Virology. 75: 9571-9578.<br /> <br /> <br /> <br /> PEER REVIEWED PUBLICATIONS (2002)<br /> <br /> <br /> Akula S, Hurley DJ, Wixon RL, Wang C, Chase CCL. 2002. Effect of genistein on replication of bovine herpesvirus type 1. Am. J. Vet. Res. 63:1124-1128.<br /> <br /> <br /> Ambagala AP, Feng Z, Barletta RG, Srikumaran S. 2002. Molecular cloning, sequencing, and characterization of bovine transporter associated with antigen processing 2 (BoTAP2). Immunogenetics. 54:30-38.<br /> <br /> <br /> Carter JN, Meredith GL, Montelongo M, Gill DR, Krehbiel CR, Payton ME, Confer AW. 2002. Relationship of vitamin E supplementation and antimicrobial treatment with acute-phase protein responses in cattle affected by naturally acquired respiratory tract disease. Am. J. Vet. Res. 63: 1111-1117.<br /> <br /> <br /> Champlin FR, Shryock TR, Patterson CE, Austin FW, Ryals PE. 2002. Prevalence of a novel capsule-associated lipoprotein among Pasteurellaceae pathogenic in animals. Curr. Microbiol. 44: 297-301.<br /> <br /> <br /> Chowdhury SI, Onderci M, Bhattacharjee PS, Al-Mubarak A, Weiss ML, Zhou Y. 2002. Bovine herpesvirus 5 (BHV-5) Us9 is essential for BHV-5 neuropathogenesis. J. Virol. 76: 3839-3851.<br /> <br /> <br /> Deshpande M, Ambagala TC, Ambagala APN, Srikumaran S. 2002. Bovine CD18 is necessary and sufficient to mediate Mannheimia (Pasteurella) haemolytica leukotoxin induced cytolysis. Infection and Immunity. 70: 5058 5064.<br /> <br /> <br /> Evermann JF, Ridpath JF. 2002. Clinical and epidemiologic observations of bovine viral diarrhea virus in the northwestern United States. Vet Microbiol. 89(2-3): 129-39.<br /> <br /> <br /> Fales-Williams AJ, Gallup JM, Ramirez-Romero R, Brogden K, Ackermann MR. 2002. Increased anionic peptide distribution and intensity during progression and resolution of bacterial pneumonia. Clin. Diagn. Lab. Immunol. 1:28-32.<br /> <br /> <br /> Fent GM, Fulton RW, Saliki JT, Caseltine SL, Lehmkuhl HD, Confer AW, Purdy CW, Briggs RE, Loan RW, Duff GC. 2002. Bovine adenovirus-7 infections in postweaning calves. Am. J. Vet. Res. 63: 976-978.<br /> <br /> <br /> Flores EF, Risatti GR, et al. 2002. Expression of the mouse Fc receptor B2 in bovine cells rescues the infectivity of conditionally neutralized bovine viral diarrhea virus. Vet. Microbiol. 85: 99-109.<br /> <br /> <br /> Frank GH, Briggs RE, Duff GC, Loan RW, Purdy CW. 2002. Effects of pretransit vaccination and arrival medication with florfenicol on the health of transported calves and the presence of Mannheimia haemolytica organisms in nasal secretions. Am. J. Vet. Res. 63: 251 256.<br /> <br /> <br /> Fulton RW, Cook BJ, Step DL, Confer AW, Saliki JT, Burge LJ, Welsh RD, Blood KS, Payton MD. 2002. Evaluation of animal health status of calves and their impact on feedot performance: Assessment of a retained ownership program of postweaning calves. Can. J. Vet. Res. 66:173-180.<br /> <br /> <br /> Fulton RW, Ridpath JF, Saliki JT, Briggs RE, Confer AW, Burge LT, Purdy CW, Loan RW, Duff GC, Payton ME. 2002. Bovine viral diarrhea virus (BVDV)1b: Predominant subtype in calves with respiratory disease. Can. J. Vet. Res. 66: 181-190.<br /> <br /> <br /> Gatto NT, Dabo SM, Hancock RE, Confer AW. 2002. Characterization of, and immune responses of mice to, the purified OmpA-equivalent outer membrane protein of Pasteurella multocida serotype A:3 (Omp28). Vet Microbiol. 87: 221-235.<br /> <br /> <br /> Geiser G, Inman M, Zhang Y, Jones C. 2002. The latency related (LR) gene of bovine herpes virus 1 (BHV 1) can inhibit the ability of bICP0 to activate productive infection. J. of General Virology. 83: 2965 2971.<br /> <br /> <br /> Gopinath RS, Ambagala APN, Hinkley S, Srikumaran S. 2002. Effects of virion host shut off activity of bovine herpesvirus 1 on MHC class I expression. Viral Immunology. 15: 595 608.<br /> <br /> <br /> Grooms DL, Coe PH. Antibody response following vaccination for respiratory viruses in preconditioned calves. Vet. Therap. 3: 119-127<br /> <br /> <br /> Grooms DL, Keilan E. 2002. Screening of neonatal calves for bovine viral diarrhea virus by immunohistochemistry on skin samples. Clin. Diagn. Lab. Immun. 9: 898-900.<br /> <br /> <br /> Guey-Chuen P, Maguen B, Jing L, Mott KR, Osorio N, Slanina SM, Yukht A, Ghiasi H, Nesburn AB, Inman M, Henderson G, Jones C, Wechsler SL. 2002. A gene capable of blocking apoptosis can substitute for the herpes simplex virus type 1 LAT gene and restore wild type reactivation levels. J. Virol. 76: 1224-1235.<br /> <br /> <br /> Harding MJ, Cao X, Shams H, Johnson AF, Vassilev VB, Wheeler DW, Haines D, Sibert GJ, Nelson LD, Campos M, Donis RO. 2002. Role of bovine viral diarrhea virus biotype in the establishment of fetal infections. Am. J. Vet. Res. 63(10): 1455 63.<br /> <br /> <br /> Inman M, Lovato L, Doster A, Jones C. 2002. A mutation in the latency related gene of bovine herpesvirus 1 disrupts the latency reactivation cycle in calves. J. of Virology. 76: 6771 6779.<br /> <br /> <br /> Jeyaseelan, S, Srinand S, Maheswaran SK. 2002. Role of Mannheimia haemolytica leukotoxin in the pathogenesis of bovine pneumonic pasteurellosis. Animal Health Research Reviews. 3: 69-82.<br /> <br /> <br /> Kelling CL, Steffen DJ, Topliff CL, Eskridge KM, Donis RO, Higuchi DS. 2002. Comparative virulence of bovine viral diarrhea virus type II in experimentally inoculated six to nine month old calves. Am. J. of Vet. Res. 63: 1379 1384.<br /> <br /> <br /> Kelling CL, Steffen DJ, Cooper VL, Higuchi DS, Eskridge KM. 2002. Effect of acute bovine viral diarrhea virus alone, bovine rotavirus alone, or concurrent infection with both on enteric disease in gnotobiotic neonatal calves. Am. J. of Vet. Res. 63: 1179 1186.<br /> <br /> <br /> Leite F, OBrien S, Sylte MJ, Page T, Atapattu D, Czuprynski CJ. 2002. Inflammatory cytokines enhance the interaction of Mannheimia haemolytica leukotoxin with bovine peripheral blood neutrophils in vitro. Infect. Immun. 70:4336-4343.<br /> <br /> <br /> Maheswaran SK, Thumbikat P, Dileepan T. 2002. Current knowledge on pathogenesis of lung injury caused by Mannheimia haemolytica and Pasteurella multocida in the bovine. In: Recent Developments and Perspectives in Bovine Medicine. p. 160-167.<br /> <br /> <br /> Pillars RA, Grooms DL. 2002. Serological evaluation of five unvaccinated heifers for detecting herds persistently infected with bovine viral diarrhea virus. Am. J. Vet. Res. 63: 499-5.<br /> <br /> <br /> Purdy CW, Straus DC, Chirase N, Parker DB, Ayers JR, Hoover MD. 2002. Effects of aerosolized endotoxin in feedyard dust on weanling goats. Small Rum. Res. 446: 133.<br /> <br /> <br /> Vanden Bush TJ, Rosenbusch RF. 2002. Mycoplasma bovis induces apoptosis of bovine lymphocytes. FEMS Immunol. Med. Microbiol. 32: 97-103.<br /> <br /> <br /> Ward ACS, Weiser GC, Delong WJ, Frank GH. 2002. Characterization of Pasteurella spp isolated from healthy domestic pack goats and evaluation of the effects of a commercial Pasteurella vaccine. Am. J. Vet. Res. 63: 119 123.<br /> <br /> <br /> Winkler MTC, A Doster, J-H Sur, C Jones. 2002. Analysis of bovine trigeminal ganglia following infection with bovine herpesvirus 1. Vet. Microbiol. 86: 139-155.<br /> <br /> <br /> <br /> ABSTRACTS (2002)<br /> <br /> <br /> Blackwood ER, Ayalew S, Confer AW. 2002. Molecular and Immunological analysis of outer membrane protein PlpE from Mannheimia haemolytica serotypes 1, 2, and 6. In 83th Annual Meeting of CRWAD. November 11-12. St. Louis, MO. Abstract nr 93.<br /> <br /> <br /> Brady RP, Topliff CL, Kelling CL. 2002. Analyses of plasmid DNA encoding the attachment glycoprotein of bovine respiratory syncytial virus. In: Conference of Research Workers in Animal Diseases Proceedings. <br /> <br /> <br /> Braun LJ, Braunschmidt M, Arias N, Wixon R, Wang CY, Chase CCL. 2002. Effect of genistein on bovine herpesvirus 1 and bovine viral diarrhea virus infections in vivo. In: 35th annual Conference of American Association of Bovine Practitioners. September 26-28. Rapid City, SD. p. 206. <br /> <br /> <br /> Dunn J, Kaneene JB, Grooms D, Bolin S, Bolin C, Bruning-Fann C. 2002. The effect of infection with Mycobacterium paratuberculosis on the reliability of the caudal fold tuberculin (CFT) test and the gamma-interferon test for bovine tuberculosis in cattle. In: Proceedings of the 83th Annual Meeting of The Conference of Research Workers in Animal Diseases. November 11. St. Louis, MO. Abstract nr 47.<br /> <br /> <br /> Elmowalid G, Ransom BL, Braun LJ, Young A, Ridpath J, Chase CCL. Bovine viral diarrhea virus interferes with macrophage surface marker expression in vitro. In: 83rd annual meeting of Conference of Research Workers in Animal Disease. November 11-12. St. Louis, MO. Abstract nr 185.<br /> <br /> <br /> Fulton RW, Step DL, Ridpath JF, Saliki JT, Confer AW, Johnson BJ, Welsh RD, Burge LJ, Hawley RV, Payton ME. 2002. Bovine Viral Diarrhea Virus (BVDV) Persistently Infected Calves: Response to Vaccinations and Diagnoses at Necropsy. 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Characterization of a lympho-inhibitory peptide produced by Mycoplasma bovis. Bioch. Biophys. Res. Comm. 315: 336-341.<br /> <br /> <br /> Welsh RD, Dye LB, Payton ME, Confer AW. 2004. Frequency of isolation and antimicrobial susceptibilities of bacterial pathogens from bovine pneumonia: 1994-2002. J. Vet. Diag. Invest. 16: 426-431.<br /> <br /> <br /> Woolums AR, Brown C, Brown Jr JC, Cole D, Scott M, Williams S, Miao C. 2004. Effects of a single intranasal dose of modified-live bovine respiratory syncytial virus vaccine on resistance to subsequent viral challenge in calves. Am. J. Vet. Res. 65: 363-372.<br /> <br /> <br /> <br /> ABSTRACTS (2004):<br /> <br /> <br /> Chase CCL, Miskimins DM, Graham T, Braun L, Steen P, Ridpath J. 2004. Evidence of bovine viral diarrhea virus persistent infection in two white-tail deer in southeastern South Dakota. In: Proceedings of the 37th annual conference of American Association of Bovine Practitioners. September 23-25. Fort Worth, TX. p. 169.<br /> <br /> <br /> Confer AW, Fulton RW, Step DL, Johnson BJ, Ridpath JF. 2004. Viral Antigen Distribution in the Respiratory Tract of Cattle Persistently Infected with Bovine Viral Diarrhea Virus Subtype 2a. At: 47th Annual Meeting of AAVLD. October 22-24. Greensboro, NC.<br /> <br /> <br /> Donovan DC, Barton MH, Norton N, Ely LO, Hurley DJ. 2004. Modulation of innate immunity by in vitro treatment of keukocytes with CD14, lactoferrin and IgG. In: Proceedings of the 84th CRWAD meeting. November 14-16. Chicago, IL. p. 39.<br /> <br /> <br /> Donovan DC, Reber AJ, Parks RJ, Collier C, Ely LO, Hurley DJ. 2004. Extracellular pH alters the innate immune response by enhancing phagocytosis and decreases reactive oxygen species production. In: American Dairy Science Annual Meeting. St. Louis, MO. J. Dairy Sci. 87 (Suppl. 1): 179.<br /> <br /> <br /> Donovan DC, Collier C, Reber AJ, Parks RJ, Hurley DJ. 2004. Extracellular pH alters immunity by decreasing the production of reactive oxygen and nitrogen species, but enhancing phagocytosis in bovine neutrophils and monocytes. In: International Conference of Production Diseases in Farm Animals. July 18-22. Michigan State University. Abstract nr A-14. <br /> <br /> <br /> Donovan DC, Reber AJ, Parks RJ, Hurley DJ. 2004. Acidic extracellular pH enhances phagocytosis and decreases reactive oxygen species production in polymorphonuclear neutrophils and monocytes. In: 7th International Veterinary Immunology Symposium. July 25-29. Quebec City, Qc, Canada. Abstract nr WK 13.6.10 p. 415. <br /> <br /> <br /> Fogarty-Fairbanks K, Rinehart CL, Ohnesorge WC, Loughin MM, Chase CCL. 2004. Fetal protection against BVDV type 1 or 2 heterologous challenge. In: Proceedings of the 37th annual conference of American Association of Bovine Practitioners. September 23-25. Fort Worth, TX. p.171.<br /> <br /> <br /> Fogarty-Fairbanks K, Campbell J, Chase CCL. 2004. Subcutaneous dose of infectious bovine rhinotracheitis virus provides early protection against an intranasal challenge. In: Proceedings of the 37th annual conference of American Association of Bovine Practitioners. September 23-25. Fort Worth, TX. p. 289.<br /> <br /> <br /> Fulton RW, Burge LJ, dOffay JM, Funk R, Weaver GD, Van Campen H, Johnson BJ. 2004. Immune Response Differences in Serums from Bovine Herpesvirus-1 Vaccinated Cattle: Depenndence of Viral Strarin. At: 47th Annual Meeting of AAVLD. October 22-24. Greensboro, NC.<br /> <br /> <br /> Fulton RW, Ridpath JF, Ores S, Saliki JT, Burge LJ, Confer AW. 2004. Bovine Viral Diarrhea Virus (BVDV) Subtypes in Diagnostic Laboratory Accessions from Clinical and Necropsy Cases: Distribution of BVDV1a, BVDV1b, and BVDV2a Subtypes. At: 47th Annual Meeting of AAVLD. October 22-24. Greensboro, NC.<br /> <br /> <br /> Gershwin LJ, Corbeil LB, Berghaus LJ, Arnold KF, Anderson ML. 2004. IgE and cytokine profiles in calves concurrently infected with BRSV and Histophilus somni. Presented at 7th International Veterinary Immunology Symposium. July. Quebec City, Canada.<br /> <br /> <br /> Hunsaker BD, Steffen DJ, Topliff CL, Kelling CL. 2004. Characterization of protection in calves from systemic infection or disease by vaccination with modified-live noncytopathic bovine viral diarrhea virus type 1. At: Conference of Research Workers in Animal Disease. <br /> <br /> <br /> Topliff, C.L., S.K.Chon, R.O. Donis, K.M. Eskridge, C.L Kelling. 2004. Translational efficiencies of the 5' untranslated region from eight genotype 2 bovine viral diarrhea virus field isolates varying in virulence. Conference of Research Workers in Animal Disease. <br /> <br /> <br /> Johnson TK, Triche PC, OReilly KL. 2004. Immune response of newborn calves to intrabronchial infection with bovine coronavirus. In: Meeting of the Louisiana Biomedical Research Network. July 28. Baton Rouge, LA.<br /> <br /> <br /> Klink HA, Brady RP, Topliff CL, Eskridge KM, Srikumaran S, Kelling CL. 2004. Influence of bovine respiratory syncytial virus F glycoprotein N-linked glycans on in vitro expression and on antibody responses in BALB/c mice. At: Conference of Research Workers in Animal Disease. <br /> <br /> <br /> Nanduri B, Lawrence ML, Burgess SC. 2004. Determination of sub-MIC effects of antibiotics on Pasteurella multocida protein expression using cleavable isotope coded affinity tag reagents. In: 104th General Meeting of the American Society for Microbiology. New Orleans, LA.<br /> <br /> <br /> Okinaga T, Hurley DJ, Woolums AR, Miao C, Zarlinga DS. 2004. Comparison of bovine cytokine gene experession as measured by competitive and real-time PCR. In: Proceedings of the 84th CRWAD meeting. November 14-16. Chicago, IL. p. 41.<br /> <br /> <br /> Okinaga T, Hines II ME, Hurley DJ. 2004. Real-time PCR measurements of cytokine mRNA from cattle and goats. In: Proceedings of the 84th CRWAD meeting. November 14-16. Chicago, IL. p. 40<br /> <br /> <br /> Wiggins M, Woolums A, Hurley DJ, Cole D, Sanchez S. 2004. The prevalence of Mycoplasma<br /> bovis in a subpopulation of Georgia cattle. In: Proceedings of the 84th CRWAD meeting. November 14-16. Chicago, IL.<br /> <br /> <br /> OReilly KL, Godeny GK, Kousoulas KG, Olcott BM, Paulsen DB, Harden TT, Smith S, Triche PC. 2004. Intrabronchial infection of newborn calves with respiratory bovine coronavirus. In: Animal Disease Research Workers of Southern States. February. Biloxi, MS.<br /> <br /> <br /> Reber AJ, Okinaga T, Tanner M, Woolums AR, Hurley DJ. 2004. Development of immunity after vaccination with MLV or killed BVD vaccines. In: Proceedings of the 84th CRWAD meeting. November 14-16. Chicago, IL. p. 40.<br /> <br /> <br /> Reber AJ, Okinaga T, Tanner M, Woolums A, Leard T, Milward F, Hurley DJ. 2004. Evaluation of multiple immune parameters during development of immunity after vaccination with MLV or killed BVD. In: 7th International Veterinary Immunology Symposium. Program and Book of Abstracts. July 25  30. Quebec City, Canada. Abstract nr WK.1.6.7. p. 150<br /> <br /> <br /> DISSERTATIONS (2004):<br /> <br /> <br /> Fogarty-Fairbanks K. 2004. New clinical applications for three USDA licensed vaccines in the prevention of infectious bovine rhinotracheitis or bovine viral diarrhea virus. Master of Science Thesis. South Dakota State University.<br /> <br /> <br /> Hassan E. 2004. Investigation of the role of viral glycoproteins gE AND gI in bovine herpesvirus type 1 (BHV-1) pathogenesis: study of cytoskeleton and phosphorylation. PhD Dissertation. South Dakota State University.<br /> <br /> <br /> Kalina WV. 2004. The influence of Alternaria alternate Aerosol on the Development of Immune Responses in Calves During a Primary and Secondary Bovine Respiratory Syncytial Virus Infection. PhD Dissertation. University of California, Davis.<br /> <br /> <br /> PEER REVIEWED PUBLICATIONS (2005)<br /> <br /> <br /> Atapattu D, Czuprynski CJ. 2005. Mannheimia haemolytica leukotoxin induces apoptosis of bovine lymphoblastoid cells (BL-3) via a caspase-9 dependent mitochondrial pathway. Infect. Immun. 73: 5504-5513.<br /> <br /> <br /> Boudreaux CM, Corstvet RE, Cooper RK, Enright FM. 2005. Effects of cecropin B transgene expression on Mannheimia haemolytica serotype 1 colonization of the nasal mucosa of calves. Am. J. Vet. Res. 66(11): 1922-1930.<br /> <br /> <br /> Carter JN, Gill DR, Lalman DL, Krehbiel CR, Confer AW, Smith RA, Claypool PL, McDowell LR. 2005. Vitamin E supplementation in the diet of newly arrived feedlot cattle. J. Anim. Sci. 83: 1924-1932.<br /> <br /> <br /> Confer AW, Fulton RW, Step DL, Johnson BJ, Ridpath JF. 2005. Viral Antigen Distribution in the Respiratory Tract of Cattle Persistently Infected with Bovine Viral Diarrhea Virus Subtype 2a. Vet. Path. 42: 192-199.<br /> <br /> <br /> Dabo SM, Confer AW. 2005. Adherence of Pasteurella multocida to fibronectin. Vet. Microbiol. 110: 265-275.<br /> <br /> <br /> Dileepan T, Thumbikat P, Walcheck B, Kannan MS, Maheswaran SK. 2005. Recombinant expression of bovine LFA-1 and characterization of its role as the receptor for Mannheimia haemolytica leukotoxin. Microbial Pathogenesis. 38: 249-257.<br /> <br /> <br /> Dileepan T, Kannan MS, Walcheck B, Thumbikat P, Maheswaran SK. 2005. Mapping of the binding site for Mannheimia haemolytica leukotoxin within the bovine CD18. Infection and Immunity. 73: 5233-5237.<br /> <br /> <br /> Doyle CK, Labruna MB, Breitschwerdt EB, Tang Y, Corstvet RE, Hergarty BC, Bloch KC, Li P, Walker DH, McBride JW. 2005. Detection of medically important Ehrlichia by quantitative multicolor TaqMan real-time polymerase chain reaction of the dsb gene. J. Mol. Diagn. 7(4): 1-7.<br /> <br /> <br /> Dunn J, Kaneene JB, Grooms D, Bolin S, Bolin C, Bruning-Fann C. 2005. Effects of positive results for Mycobacterium avium subsp. paratuberculosis as determined by microbial culture of feces or antibody ELISA on results of caudal fold tuberculin test and interferon-gamma assay for tuberculosis in cattle. Am. J. of Vet. Res. 226: 429-435.<br /> <br /> <br /> Fulton RW, Briggs RE, Ridpath JF, Saliki JT, Confer AW, Payton ME, Duff GC, Step DL, Walker D. 2005. Transmission of bovine viral diarrhea virus 1b to susceptible and vaccinated calves by exposure to persistently infected calves. Can. J. Vet. Res. 69: 161-169.<br /> <br /> <br /> Fulton RW, Ridpath JF, Ore S, Confer AW, Saliki JT, Burge LJ, Payton ME. 2005. Bovine viral diarrhoea virus (BVDV) subgenotypes in diagnostic laboratory accessions: Distribution of BVDV1a, 1b, and 2a subgenotypes. Vet. Microbio. 111: 35-40.<br /> <br /> <br /> Geiser V, Jones C. 2005. Localization of sequences within the latency related gene of bovine herpesvirus 1 that inhibit mammalian cell growth. J. of Neurovirology. 11: 563-570.<br /> <br /> <br /> Geiser V, Zhang Y, Jones C. 2005. Analysis of a bovine herpesvirus 1 (BHV-1) recombinant virus that does not express the bICP0 protein. J. of General Virology. 86: 1987-1996.<br /> <br /> <br /> Hollis LC, Smith JF, Johnson BJ, Kapil S, Mosier DA. 2005. A comparison of serological responses when modified-live infectious bovine rhinotracheitis virus vaccine, Mannheimia haemolytica bacterin-toxoid are administered with needle-free versus conventional needle-based injection in yearling feedlot steers. The Bovine Practitioner. 39: 106-109. <br /> <br /> <br /> Hollis LC, Smith JF, Johnson BJ, Kapil S, Mosier DA. 2005. A comparison of serological responses when modified-live infectious bovine rhinotracheitis virus vaccine, Mannheimia haemolytica bacterin-toxoid and Leptospira pomona bacterin are administered with needle-free versus conventional needle-based injection in Holstein dairy calves. The Bovine Practitioner. 39: 110-114.<br /> <br /> <br /> Kuckleburg C, Sylte MJ, Inzana TJ, Corbeil LB, Darien B, Czuprynski CJ. 2005. Bovine platelets activated by Haemophilus somnus or its lipooligosaccharide cause endothelial cell damage in vitro. Microb. Pathogen. 38: 23-32. <br /> <br /> <br /> Larson RL, Brodersen BW, Grotelueschen DM, Hunsaker BD, Burdett W, Brock KV, Fulton RW, Goehl DR, Sprowls RW, Kennedy JA, Lonergan GH, Dargatz DA. 2005. Consideration for bovine viral diarrhea (BVD) testing. Bov. Practitioner. 39: 96-100.<br /> <br /> <br /> Muhammad-Tahir Z, Alocilja EC, Grooms DL. 2005. Rapid detection of bovine viral diarrhea virus as surrogate of bioterrorism agents. IEEE Sensors Journal. 5(4): 757-762.<br /> <br /> <br /> Perez S, Inman M, Doster A, Jones C. 2005. The latency related gene encoded by bovine herpesvirus 1 (BHV-1) promotes virus growth and reactivation from latency in tonsils of infected calves. J. of Clin. Microbio. 43: 393-401.<br /> <br /> <br /> Petit C.M, Melancon J.M, Chouljenko VN, Colgrove RC, Farzan M, Knipe D.M, Kousoulas KG. 2005. Genetic analysis of the SARS-coronavirus spike glycoprotein functional domains involved in cell-surface expression and cell-to-cell fusion. Virology. 341: 215-230.<br /> <br /> <br /> Prado ME, Dabo SM, Confer AW. 2005. Immunogenicity of iron-regulated outer membrane proteins of Pasteurella multocida A:3 in cattle: molecular characterization of the immunodominant heme acquisition system receptor (HasR) protein. Vet. Microbiol. 105: 269-280.<br /> <br /> <br /> Qiu Z, Zhu J, Harms JS, Friedrichsen J, Splitter GA. 2005. Bovine herpesvirus VP22 induces apoptosis in neuroblastoma cells by upregulating the expression ratio of Bax to Bcl-2. Hum. Gene Ther. 16: 101-108. <br /> <br /> <br /> Reber AJ, Hippen AR, Hurley DJ. 2005. Ingestion of whole colostrum rapidly induces the capacity in newborn calves to stimulate and respond in one-way mixed leukocyte cultures. Am. J. Vet. Res. 66: 1854-1860.<br /> <br /> <br /> Reeks BY, Champlin FR, Paulsen DB, Scruggs DW, Lawrence ML. 2005. Effects of sub-MIC antibiotic levels and temperature on growth kinetics and outer membrane protein expression in Mannheimia haemolytica and Haemophilus somnus. Can. J. Vet. Res. 69: 1-10.<br /> <br /> <br /> Step DL, Confer AW, Kirkpatrick JG, Richards JB, Fulton RW. 2005. Respiratory Tract Infections in Dairy Calves from Birth to Breeding Age: Detection by Laboratory Isolations and Seroconversions. Bovine Practitioner. 39: 44-532.<br /> <br /> <br /> Sylte MJ, Kuckleburg CJ, Corbei LB l, Inzana TJ, Bertics PJ, Czuprynski CJ. 2005. Stimulation of P2X7 enhances Haemophilus somnus lipooligosaccharide-mediated apoptosis of endothelial cells. J. Leuk. Biol. 77: 958-965. <br /> <br /> <br /> <br /> Sylte MJ, Kuckleburg CJ, Leite FP, Inzana TJ, Czuprynski CJ. 2005. Interleukin-1 beta diminishes Haemophilus somnus¬ lipooligosaccharide-mediated apoptosis of endothelial cells. Microb. Pathogen. 39: 121-130.<br /> <br /> <br /> Tahir ZM, Alocilja EC, Grooms DL. 2005. Polyaniline synthesis and its biosensor application.<br /> Biosens Bioelectron. 20(8): 1690-1695.<br /> <br /> <br /> Tatum FM, Yersin YG, Briggs RE. 2005. Construction and virulence of a Pasteurella multocida FhaB2 mutant in turkeys. Microb Pathog. 39(1-2): 9-17.<br /> <br /> <br /> Thumbikat P, Dileepan T, Kannan MS, Maheswaran SK. 2005. Mechanisms underlying Mannheimia haemolytica leukotoxin-induced oncosis and apoptosis of bovine leukocytes. Microbial Pathogenesis. 38: 161-172.<br /> <br /> <br /> Thumbikat P, Dileepan T, Kannan MS, Maheswaran SK. 2005. Characterization of Mannheimia (Pasteurella) haemolytica leukotoxin interaction with bovine alveolar macrophage b2 integrins. Vet. Research. September Issue.<br /> <br /> <br /> Topliff CL, Chon SK, Donis RO, Eskridge KM, Kelling CL. 2005. In vitro and in vivo translational efficiencies of 5' untranslated region from eight genotype 2 bovine viral diarrhea virus isolates. Virology. 331: 349-356.<br /> <br /> <br /> Woolums AR, Loneragan GH, Hawkins LL, Williams SM. 2005. Baseline management practices and animal health data reported by U.S. feedlots responding to a survey regarding acute interstitial pneumonia. Bov. Pract. 39: 116-124.<br /> <br /> <br /> Woolums AR, Loneragan GH, Hawkins LL, Williams SM. A survey of the relationshiop between management practices and risk of acute interstitial pneumonia at U.S. feedlots. Bov Pract; 39:125-133; 2005.<br /> <br /> <br /> Zhang Y, Jones C. 2005. Identification of functional domains within the bICP0 protein encoded by BHV-1. J. of General Virology. 86: 879-886.<br /> <br /> <br /> Zhu J, Qiu Z, Wiese C, Ishii Y, Friedrichsen J, Rajashekara G, Splitter GA. 2005. Nuclear and mitochondrial localization signals overlap within bovine herpesvirus 1 tegument protein VP22. J. Biol. Chem. 280: 16038-16044.<br /> <br /> <br /> ABSTRACTS (2005):<br /> <br /> <br /> Ayalew S, Blackwood ER, Confer AW. 2005. Sequence diversity of the immunogenic outer membrane lipoprotein PIpE from Mannheimia haemolytica serotypes 1, 2 and 6. In: Proceedings 105th Annual Meeting of American Society of Microbiology. Atlanta, GA.<br /> <br /> <br /> Dabo SM, Anderson BE, Confer AW, Gupta S. 2005. Expression, Purification and Binding Activity of B. henselae Pap 31. In: Proceedings 105th Annual Meeting of American Society of Microbiology. Atlanta, GA.<br /> <br /> <br /> Lawrence ML. 2005. Impact of sub-MIC levels of chlortetracycline and chlortetracycline/ sulfamethazine on growth kinetics of Mannheimia haemolytica and Haemophilus somnus. Summer 2005 Academy Of Veterinary Consultants Conference. Kansas City, MO.<br /> <br /> <br /> Nanduri B, Burgess SC, Lawrence ML. 2005. Sub-MIC concentrations of antibiotics decrease Mannheimia haemolytica leukotoxin expression. At: 105th General Meeting of the American Society for Microbiology. Atlanta, GA.<br /> <br /> <br /> Nanduri B, Lawrence ML, Burgess SC. 2005. Proteomic profiling of M. haemolytica; a bacterial pathogen with a draft genome. At: 53rd ASMS Conference on Mass Spectrometry. San Antonio, TX.<br /> <br /> <br /> Tigabu B, Chase CCL, Braun LJ. 2005. BVDV influences the expression of Toll-like receptors. Abstract W13-4. At: 24th Annual Meeting of American Society for Virology. June 18-22. University Park, PA.<br /> <br /> <br /> <br /> BOOK CHAPTER (2005)<br /> <br /> <br /> Goyal S, Ripdath JF, editors. 2005. Vaccines. In: Bovine Viral Diarrhea Virus: Diagnosis, Management and Control. Blackwell Publishing: Ames, IA. p. 209-222.<br /> <br /> <br /> <br /> PEER REVIEWED PUBLICATIONS (2006)<br /> <br /> <br /> Ayalew S, Blackwood ER, Confer AW. 2006. Sequence diversity of the immunogenic outer membrane lipoprotein PipE from Mannheimia haemolytica serotypes 1, 2, and 6. Vet. Microbiol. 114: 260-268.<br /> <br /> <br /> Behling-Kelly E, Vonderheid H, Kim KS, Corbeil LB, Czuprynski CJ. 2006. Roles of cellular activation and sulfated glycans in Haemophilus somnus adherence to bovine brain microvascular endothelial cells. Infect. Immun. 74: 5311-5318.<br /> <br /> <br /> Brock KV, McCarty K, Chase CCL, Harland R. 2006. Protection against fetal infection with either bovine viral diarrhea virus type 1 or type 2 using a non-cytopathic type 1 modified live virus vaccine. Vet. Therapeutics. 7: 27-34.<br /> <br /> <br /> Chan D, Cohen J, Naito J, Mott KR, Osorio N, Jin L, Fraser NW, Jones C, Wechsler SL, Chuen Perng G. 2006. A mutant deleted for most of the herpes simplex virus type 1 (HSV-1) UOL gene does not affect the spontaneous reactivation phenotype in rabbits. J. of Neurovirology. 12: 5-16.<br /> <br /> <br /> Chowdhury SI, Mahmood S, Simon J, Al-Mubarak A, Zhou Y. 2006. The Us9 gene encoded by bovine herpesvirus type 1 (BHV-1) effectively complements a Us9-null bovine herpesvirus 5 (BHV-5) for anterograde transport, neurovirulence and neuroinvasiveness in a rabbit model. J. Virol. 80: 4396-4405. <br /> <br /> <br /> Confer AW, Ayalew S, Panciera RJ, Montelongo M, Wray JH. 2006. Recombinant Mannheimia haemolytica serotype 1 outer membrane protein PIpE enhances commercial M. haemolytica vaccine-induced resistance against serotype 6 challenge. Vaccine. 24: 2248-2255.<br /> <br /> <br /> Fulton RW, Johnson BJ, Briggs RE, Ridpath JF, Salliki JT, Confer AW, Burge LJ, Step DL, Walker DA, Payton ME. 2006. Challenge with bovine viral diarrhea virus by exposure to persistently infected calves: Protection by vaccination and negative results of antigen testing in acutely infected calves. Can. J. for V. Res. 70: 1-127.<br /> <br /> <br /> Fulton RW, Hessman B, Johnson BJ, Ridpath JF, Saliki J, Burge LJ, Sjeklocha D, Confer AW, Funk R, Payton ME. 2006. Evaluation of diagnostic tests used for detection of bovine viral diarrhea virus and prevalence of BVDV subtypes 1a, 1b, and 2a in persistently infected cattle entering a feedlot. J. of Am. Vet. Med. Assoc. 228: 578-584.<br /> <br /> <br /> Jones C, Geiser V, Henderson G, Jiang Y, Meyer F, Perez S, Zhang Y. 2006. Functional analysis of bovine herpesvirus 1 (BHV-1) genes expressed during latency. Vet. Microbio. 113: 199-210.<br /> <br /> <br /> Prado ME, Confer AW, Prado TM. 2006. Maternally-and naturally-acquired antibodies to Mannheimia haemolytica and Pasteurella multocida in beef calves. Vet. Immunol. & Immunopathol. 111: 301-307.<br /> <br /> <br /> Reber AJ, Tanner M, Okinaga T, Woolums AR, Williams S, Ensley DT, Hurley DJ. 2006. Evaluation of multiple immune parameters during development of immunity after vaccination with modified live virus or killed bovine viral diarrhea virus vaccines. Comp. Immunol. Microbiol. & Inf. Dis. 29: 61-77.<br /> <br /> <br /> Reber AJ, Hippen AR, Hurley DJ. 2006. Colostral whey alters the expression of activation and trafficking markers on bovine mononuclear cells in vitro. Vet. Immunol. Immunopathol. 109: 139-150.<br /> <br /> <br /> Rogers D, Wyatt C, Walz P, Drouillard J, Mosier D. 2006. Bovine alveolar macrophage<br /> neurokinin -1 and response to substance P. Vet. Immunol. Immunopathol. 112: 290-295.<br /> <br /> <br /> Sylte M, Inzana T, Czuprynski CJ. 2006. Role of tumor necrosis factor in endothelial cell apoptosis caused by Haemophilus somnus lipooligosaccharide. Vet. Immunol. Immunopathol. 110: 303-309.<br /> <br /> <br /> Zhang Y, Jiang Y, Zhou J, Geiser V, Jones C. 2006. The bovine herpes virus 1 (BHV-1) immediate early protein (bICP0) interacts with the histone acetyltransferase p300, and these interactions correlate with stimulation of gC promoter activity. J. of Gen. Virology. 87: 1843-1851.<br /> <br /> <br /> Zimmerman A, Boots R, Valli L, Chase CCL. 2006. Maternal antibody BVDV positive calves vaccinated with a modified live bovine viral diarrhea virus (BVDV) vaccine are protected against a virulent BVDV type 2 challenge. JAVMA 228: 1757-61.<br />

Impact Statements

1. Impact statements (2001-2006): Bovine respiratory disease is a significant problem to the cattle industry. BHV-1, BVDV, and BRSV are important pathogens of cattle. Studies focused on understanding the replication of these viruses, and developing better vaccines are crucial for the cattle industry.
2. Impact statements (2001-2006) Continued: The data on the association between fever and M. bovis shedding indicate to veterinarians and producers that M. bovis shedding is likely related to an inflammatory condition in backgrounding/stocker cattle. Veterinarians and producers should pay careful attention to cattle at risk for shedding M. bovis so that timely intervention of affected animals can be initiated to minimize losses due to illness in these cattle. Different isolates of M. bovis vary in their ability to impair the host immune response, so limiting the number of isolates that cattle are exposed to via management practices should minimize the negative impact of M. bovis on host immunity.
3. Impact statements (2001-2006) Continued: The data on the impact of cellular components of colostrum on neonatal immunity provide to veterinarians and producers proof that not only antibody but also the cells contained in colostrum are important in ensuring a strong and effective immune response in neonatal calves. Improvements in methods of colostrum handling that preserve the cellular components should be developed to improve neonatal immune responses to infectious disease.
4. Impact statements (2001-2006) Continued: The data on the effect of acidosis on immune cell function prove to veterinarians and producers that diseases associated with acidosis have a negative impact on host immunity, potentially increasing susceptibility of cattle to infectious agents. The data indicate that management practices that limit the development of acidosis may also have financial benefit to producers by limiting infectious disease.
5. Impact statements (2001-2006) Continued: The data from genomic fingerprinting and antimicrobial susceptibility profiles of Mycoplasma bovis isolates to determined that infections with this mycoplasma are predominantly by a single strain, and that the same strain can be found in the upper and lower respiratory tract of a bovine. Large variations among surface antigens of M. bovis strains would require development of ELISA serology tests directed to conserved surface antigens.
6. Impact statements (2001-2006) Continued: Iowa has shown that the immunosuppressive activity seen with Mycoplasma bovis is due to a C-terminal peptide of a surface exposed protein of the mycoplasma. The immunosuppressive peptide is a conserved surface antigen.
7. Impact statements (2001-2006) Continued: The immune response to Mycoplasma bovis infection was shown to be Th-2 biased, and included a component of innate immune responses from gamma-delta lymphocytes.
8. Impact statements (2001-2006) Continued: Bovine herpesvirus eastablishes life long latency from primary infection. A latent infection is established in sensory neurons following acute infection. However, the virus can reactivate and spread to other cattle. Reactivation from latency and transport to primary infection site and virus shedding is the mechanism by which the virus survives in nature and is thus an important property of pathogenesis.
9. Impact statements (2001-2006) Continued: Information gained from the work is useful for designing an effective vaccine against BHV-1 that is more immunogenic compared to the entire gE-deleted BHV-1.Yet they are safe because they are attenuated and defective in anterograde transport and therefore are not shed from the eye and nose following reactivation.
10. Impact statements (2001-2006) Continued: Findings of the study indicate that the antimicrobial peptide cecropin B continues to be useful in inhibiting M. haemolytica colonization. The use of gene therapy will help to eliminate primary M. haemolytica infection in cattle destined for the feedlots. This work will aid in the development of novel strategies for control of shipping fever.
11. Impact statements (2001-2006) Continued: Field studies with naturally occurring disease are useful to identify multiple viral etiologies interacting with M. haemolytica and P. multocida. Also these field studies permit evaluation of current viral and bacterial vaccines along with newly developed vaccines. The identification, cloning, and production of subunit components of M. haemolytica and P. multocida offer opportunity for new bacterial vaccines to control BRD.
12. Impact statements (2001-2006) Continued: As an outcome of our NC107 project, the critical amino acid residues encompassing the leukotoxin binding site within the bovine CD18 will be identified. This will allow us to design agents that can interrupt LktA-CD18 interaction in bovine leukocytes and abrogate the host inflammatory responses leading to pneumonia.

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