Brief Summary of Minutes of Annual Meeting

NC-1027 An Integrated Approach to the Control of Bovine Respiratory Disease Annual Report, 2009 Annual Meeting: In conjunction with 2009 BRD Symposium, Colorado Springs, CO; August 6, 2009. Stations reporting: Georgia, Iowa, Kansas, Michigan, Nebraska, Oklahoma, South Dakota, Wisconsin Stations attending: Georgia (Woolums), Iowa (Rosenbusch), Michigan (Grooms), Nebraska (McVey), Oklahoma (Fulton), South Dakota (Chase), Wisconsin (Czuprynski) Guests: Dr. Peter Johnson (USDA CSREES), Dr. Eileen Thacker (USDA ARS), Dr. Bob Briggs (USDA NADC), Dr. Maria Prado Agenda: 7:30 PM Welcome 7:35 PM Discussion on BRDC meeting and outcomes from the meeting and Open Forum at AABP 8:35 PM Future of NC1027- 9:30 PM Adjourn Discussion of the BRD Symposium which ended this evening. Consensus is that meeting was a great success. Many positive comments from attendees to membership. Dr. Woolums will talk to Dr. Gyles of Animal Health re publication of proceedings. Options for profit: will try to put over in rolling account at University of Georgia. If this is a problem, may keep money with Dr. Jim Roths organization; outside of Iowa State. BVD group did this with their profit. What to do with profit: Dr. Fulton suggests organizing committee should get what speakers got (for reimbursement and honorarium). Once bills are paid will discuss options further, possibilities include student research awards at national meetings, or save money for next Symposium. Breakout session summaries: Dr. Rosenbusch will summarize. Where to put it? Would be ideal to keep with proceedings in AHRR if Dr. Gyles will accept it. That will be our first plan. Were planning a bulleted list; AHRR may want different format. Proceedings: some still available. Will make available on website for $15. Will charge the same for pdf on CD. Open Forum on BRD at AABP: was a big success last year; about 60-70 AABP attendees came to have informal discussion. Drs. Chase, Grooms, Woolums are on new Bovine Respiratory Disease Committee, which is scheduled to meet Thur AM of AABP meeting. Dan points out that much competition for that time. Dan Grooms will talk to Gatz Riddell re possibility of meeting at another time. Will ask Gatz if we can put flyer in registration packets as in past. Discussion of future of NC-1027: consensus was that poor attendance in recent years has been disappointing. Discussion of possibilities of terminating group and founding a Ruminant Respiratory Disease Society. Consensus that no great loss if group ended since very few get any money for involvement any more, and those that do will be able to get money by other routes through their AES. Downside to ending project: we may have no more impetus to meet, which is good opportunity for sharing research info and discussing research collaboration possibilities. Dr. Peter Johnson offered to require AFRI awardees funded for BRD research to present annually in conjunction with our annual meeting as a Society or other format. This would help maintain drive for scientific presentations. Some discussion of annually meeting in conjunction with CRWAD, but majority felt that good to meet with AABP because this gives researchers opportunity to interact with private practitioners, to possible benefit of both parties. Dr. Johnson reminded us that if we maintain multistate project we can invite with reason anyone to join committeedo not have to be only people at AESs. Even those from outside of U.S. OK; Dr. Hahn would have to approve but Dr. J thinks probably not a problem. Dr. Chase will talk to his AES director about pros/cons and logistics of terminating project early and will report back. If we do terminate, plan to pursue Ruminant Respiratory Disease Society. Plan for meeting: meet next year at AABP. Come up with new name. Send out invitation to all interested parties. Tell them to meet at AABP. AFRI will let BRD awardees know they need to present in conjunction with our meeting. Remember if we are a multistate next year we can still invite anyone we want. Some discussion: what to have AFRI awardees do, poster or presentation? Many felt presenting at AABP poster session would be best. Consensus is that we should have 1) meeting of society at AABP; 2) ask AABP for a recurring block for oral presentations in Research Session, and have a selected number of AFRI awardees present as well as some Society members; 3) rest of AFRI awardees present poster Peter Johnson will tell AFRI awardees to block off Aug 18-22 and plan to present there; more details to follow Update re CAP from Dr. Johnson: there will be new CAP project funded, RFP will be in 2010, will be openmight identify certain diseases or issues, but could be broad, too. Could request individuals to put in applications, then some internal committee would decide which to put forth. Will only have one at a time, may have every other year. How much/durationmaybe 1.5 million for 4 years. This would fit well with budget. Remember re CAP: project director has to dedicate 35-40% of their time to managing CAP, especially in first year. Need administrative assistant with a good salarynot a $15k/y person! Project director needs to have even keeled personality, someone who community trusts. Ideally they would not receive any money except for salary support so those who apply for funding in CAP dont think they have conflict of interest. Remember project has to be integratedfrom d. 1, extension has to be an objective; need education component, too (sounds like this is part of outreach). Have an extension specialist who is co-PD and who manages that objective. So have research team and outreach team and both have to be strong. No more than 2/3 of budget can go to any one of these elements. Have an external scientific review board WHO WILL NOT BE FUNDED BY CAP review the submitted proposals. Then no hard feelings between members and project director. Q: can education be at any level? Yes, even 4-H involvement can work! Challenging thing is that community is large, but not everyone can get money. They do have developmental grants every year so new people can join. Can talk to PRRSV people for info. Remember each year there is a reviewscientific board reviews progress periodically. PRRSV and Johnes: stakeholder board has final say. So far they havent vetoed anything. Q: could former CAP members apply for something new (new disease)? Yes. Is one of the current CAPs ending? No. Definitely look at how PRRSV and Johnes have worked. PRRSV CAP 2 is different than PRRSV CAP 1. Johnes is very different. Middle of Nov is target AFRI RFI, letters of intent will probably be due in Jan 10; deadlines for upcoming year will probably be similar to last year.

Accomplishments: Objective 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. Identification of various BRSV strains by commercial human RSV diagnostic kits: Georgia has provided BRSV isolates for testing in this project being carried out by Michigan. The utility of physiologic, behavioral and pathological changes as objective indicators of early respiratory disease in calves with experimental M. haemolytica pneumonia were examined. Temperature, pulse, respiration, clinical illness score, activity level (pedometers and accelerometers) respiratory character, arterial blood gas, blood chemistry and complete blood counts were assessed. Routine laboratory parameters and subjective measures were not reliable indicators of progression of pneumonia. However activity, objectively measured with pedometers and accelerometers, appears to be a promising tool for early recognition of bovine respiratory disease. BVDV PI Cattle Monitoring in the Feedyard; Surveillance for the PI cattle entering a southwest Kansas feedlot has continued since July 1, 2004 through November 2008. The PI cattle based on the positive tests of ACE and IHC from ear notches had serums collected, virus propagated in cell culture and sequenced with BVDV subtypes determined. Since 2004 through 2008, 1280 PI cattle have had the viruses subtyped with the distribution of subtypes: BVDV1b, 1003 (78.4%); BVDV1a, 154 (12.0%); and BVDV2a, 123 (9.6%). The USDA, ARS, NADC provided extensive collaboration by sequencing the viruses. OSU also provided an OSU monoclonal antibody to BVDV to the USDA laboratory of Dr. Julia Ridpath. Multiple diagnostic tests to identify cattle with bovine viral diarrhea virus and duration of positive test results in persistently infected cattle: Several tests for bovine viral diarrhea virus (BVDV) were applied to samples collected from twelve persistently infected (PI) cattle with BVDV subtypes of U.S. cattle: BVDV1a, BVDV1b, and BVDV2a. These collections were made monthly from December 20, 2005 through November 27, 2006 (day 0 to day 342). The samples collected included clotted blood for serums, nasal swabs, and fresh and formalin-fixed ear notches. The tests utilized included viral titration of nasal swabs and serums for infectious virus; antigen-capture ELISA (ACE) on fresh ear notches, serums, and nasal swabs; gel-based polymerase chain reaction (PCR) on serums, nasal swabs, and fresh ear notches; immunohistochemistry (IHC) on formalin-fixed notches; and serology for BVDV antibodies in serums. Of the twelve animals starting the study, three died with Mucosal disease. The IHC and ACE tests on ear notches were positive throughout the study as were the serums for ACE and PCR. There was detectable virus in nasal swabs of all cattle throughout the study with the exception of a few that were toxic to cell cultures. The serums had viral titers e log10 1.6 in all samples of all PI cattle, except for three collections of one animal. PCR testing of individual samples were most often positive, although there were several with equivocal results. The BVDV antibodies were due to vaccination or exposure to heterologous PI strains, and did not appear to interfere with any BVDV test. These studies illustrate that PI cattle may be identified by several tests, yet differentiation of PI cattle from acute BVDV infections of cattle will require additional testing, especially for blood samples and nasal swabs positive on initial test. Also, calves PI with BVDV are continual shedders of infectious virus as shown by infectivity of nasal swab samples over the 11-month study. Evaluation of economic effects and the health and performance of the general cattle population after exposure to cattle persistently infected with bovine viral diarrhea virus in a starter feedlot: The objectives of the study were to investigate the economic effects and health and performance of the general cattle population after exposure to cattle persistently infected (PI) with bovine viral diarrhea virus (BVDV) in a feedlot. There were 21,743 high-risk calves from the southeastern United States in a commercial feedlot. The PI status was determined by use of an antigen-capture ELISA (ACE) and confirmed by use of a second ACE, reverse transcriptasePCR assay of sera, immunohistochemistry of skin samples for BVDV antigen, and virus isolation from sera. Groups with various amounts of exposure to BVDV PI cattle were used. After being placed in the feedlot, identified PI cattle were removed from 1 section, but PI cattle remained in another section of the feedlot. Exposure groups for cattle lots arriving without PI animals were determined by spatial association to cattle lots, with PI animals remaining or removed from the lot. There were 15,348 cattle that maintained their exposure group. Performance outcomes improved slightly among the 5 exposure groups as the risk for exposure to BVDV PI cattle decreased. Health outcomes had an association with exposure risk that depended on the exposure group. Comparing cattle lots with direct exposure with those without direct exposure revealed significant improvements in all performance outcomes and in first relapse percentage and mortality percentage in the health outcomes. Economic analysis revealed that fatalities accounted for losses of $5.26/animal and performance losses were $88.26/animal. This study provided evidence that exposure of the general population of feedlot cattle to BVDV PI animals resulted in substantial costs attributable to negative effects on performance and increased fatalities. In South Dakota and Wisconsin, the infectious agents associated with bovine respiratory disease complex were monitored by bacterial culture, virus isolation, and fluorescent antibody techniques. Objective 2: To investigate the basic biology, molecular pathogenesis, and immunopathogenesis of polymicrobial infections including important viral and bacterial agents. Development of primary bovine bronchial epithelial cell (BBEC) cultures from cells taken from living cattle by bronchial brushing: This project is slowly ongoing. The in vitro effects of substance P alone or in combination with TNF, LPS, and/or histamine on bovine endothelial cell cultures were investigated. Permeability of endothelial cultures was determined by diffusion of albumin bound to Evans Blue dye through and endothelial monolayer cultured on a permeable membrane. The permeability of microvascular endothelium increased the greatest after stimulation with a combination of substance P and histamine. Responses to substance P and histamine alone were less than the combination, but equal to each other. Permeability of macrovascular endothelium increased the greatest after stimulation with a combination of substance P and LPS. The permeability induces by a substance P/histamine combination was slightly less than that produced by substance P/LPS, and the least stimulation occurred with substance P, TNF and LPS alone. Functional analysis of bICPO, a bovine herpesvirus 1 gene that is a promiscuous transactivator: bICP0 can activate expression of all three classes of viral genes, is expressed throughout productive infection, and is thus considered to be the most important viral regulatory gene. We have demonstrated that a C3HC4 zinc ring finger near the amino terminus of bICP0 plays an important role in activating transcription and productive infection. Furthermore, bICP0 interacts with chromatin remodeling enzymes {histone deacytlase 1 (HDAC1) and a histone acetylase (p300)}. Recent studies have demonstrated that bICP0 also inhibits interferon dependent transcription, suggesting that bICP0 regulates innate immune responses. Regulation of the latency-reactivation cycle by the bovine herpesvirus 1 latency related (LR) gene: Like other members of this subfamily, a latent infection is established in sensory neurons following acute infection. However, the virus can reactivate and spread to other cattle. Reactivation from latency is the mechanism by which the virus survives in nature and is thus an important property of pathogenesis. During a latent infection, one abundant viral transcript can be detected; the latency related RNA (LR-RNA). Expression of LR proteins is necessary for reactivation from latency and protecting infected neurons from apoptosis. We have demonstrated that a LR encoded protein (ORF-2) or ORF-2 fusion proteins encoded by alternatively spliced LR transcripts inhibit cold shock or Fas ligand induced apoptosis in mouse neuroblastoma cells (neuro-2A). Frame shift mutants of ORF-2 do not inhibit apoptosis suggesting that protein expression, not LR-RNA expression, mediates the anti-apoptosis activity of the LR gene in transfected neuro-2A cells. Yeast two-hybrid analysis has revealed that ORF-2 sequences specifically interact with two cellular proteins that regulate cell survival and differentiation (Notch 1 and Notch 3). We have also identified sequences in the LR gene that inhibit bICP0 expression. It appears that a viral encoded micro-RNA may inhibit bICP0 expression. Mannheimia haemolytica immunity of cattle following vaccination with chimeric protein: This study was done to determine if intranasal vaccination of young Holstein calves with a chimeric protein containing the immunodominant surface epitope of Mannheimia haemolytica PlpE (R2) and the neutralizing epitope of leukotoxin (NLKT) in the presence cholera toxin (CT) could stimulate secretory and systemic antibodies against M. haemolytica antigens. Dairy calves ranging from 3 to 18 days old were intranasally vaccinated with PBS, 10 or 100 µg of M. haemolytica chimeric protein SAC89, which contains two copies each of R2 and of NLKT, with 20 µg of CT. Vaccination with either concentration of SAC89 stimulated significant (p < 0.05) increases in intranasal IgA antibodies to PlpE and to LKT, whereas significant increases (p < 0.05) in serum antibodies were only demonstrated against M. haemolytica whole bacterial cells in the 10 µg SAC89 concentration group. Therefore, intranasal vaccination with R2-NLKT chimeric protein plus CT enhanced mucosal antibody responses to M. haemolytica PlpE and LKT. Further studies are needed to determine if this intranasal vaccination is a viable method for stimulating protection of young dairy calves against M. haemolytica. The effect of BVDV on innate immunity in the developing fetus: This project is part of a collaborative project between South Dakota and Dr. Thomas Hanson of Colorado State University. We have developed a method to access macrophage activity in the fetal calf using Kueffer Cells from the liver. These studies are looking at fetuses at different gestarion lengths and the effect on innate immunity. The effect of BVDV on macrophage cytoskeleton. This project has just begun but is using 5 different NCP BVDV strains and determining their effect on actin and microtubule architecture. During the past year Wisconsin ontinued to investigate intracellular pathways that result in bovine lymphoblastoid (BL3) cell death following exposure to M. haemolytica LKT. Experiments confirm that LKT is also transported to mitochondria in bovine peripheral blood neutrophils and monocytes. However we find some differences in what mitochondrial proteins bind LKT, and in the ability of cyclosporine to prevent LKT binding to mitochondria. A student in the lab designed an LKT construct to track internalization and transport of LKT in leukocytes. This effort was aided by Dr. Maheswaran at Minnesota. We also reported that brief heating of LKT increases its cytotoxic potency for bovine leukocytes and eliminates the strict species-specific toxicity of the native toxin. Heating of the related RTX toxin, the E. coli hemolysin, similarly increases its cytotoxicity for target cells. It is clear from both field observations and experimental studies that active infection with BHV-1 or other bovine respiratory viruses predisposes cattle to more severe pneumonia with M. haemolytica. We have evidence that infection of primary bovine bronchiolar epithelial cell lines with BHV-1 increases the adhesion of M. haemolytica to these cells. Likewise it also increases the adherence of bovine neutrophils to the viral-infected epithelial cells. Conditioned medium from BHV-1 infected epithelial cells increases neutrophil adhesion to uninfected epithelial cells. We also find that BHV-1 infection increases epithelial cell expression of IL-8, and several inflammatory cytokines (IL-1a, IL-1b, TNF-a). We showed that conditioned medium from BHV-1 infected epithelial cells is chemotactic for bovine PMNs, and activates PMN oxidative burst and expression of CD11a/CD18. The latter is associated with increased killing by M. haemolytica LKT. These studies have been assisted by scientists at the Nebraska Medical Center. Wisconsin compared the responses of bovine pulmonary epithelial and endothelial cells to LPS and LKT. Endothelial cells are more responsive to LPS, exhibiting changes in transepithelial electrical resistance (TEER), expression of inflammatory cytokines, and morphologic and biochemical changes consistent with apoptosis. Epithelial cells also produced inflammatory cytokines in response to LPS, but did not demonstrate decreased TEER or cytotoxic changes, unless activated neutrophils were included in the incubation mixture. Both epithelial and endothelial cells had similar TLR-4 mRNA levels, suggesting that other differences in signaling are responsible for the dichotomy in response to LPS between the two cell types. ATP has also been examined as a potential mediator of changes to respiratory epithelial and endothelial cells. Our results show that ATP causes rapid but reversible morphologic changes in epithelial but not endothelial cells. In contrast, both epithelial and endothelial cell monolayers exhibit increased permeability as measure by electrical conductance TEER) following incubation with micromolar concentrations of ATP in vitro. Wisconsin also continued their studies of mechanisms by which Haemophilus somnus causes vasculitis. The most severe manifestation of H. somnus infection is thrombomeningoencephalitis (TME). Cerebral microvascular endothelial cells are the primary cellular constituent of the blood brain barrier, which protects the central nervous system from inflammation and infectious agents. Recent results indicated that incubation of brain microvascular endothelial cells with H. somnus increases their surface expression of PECAM-1 and eNOS. We hypothesize that these events might contribute to platelet and neutrophil adhesion to endothelial cellsPECAM-1) and increased vascular permeability (eNOS). Consistentwith this inferecen we show that PMN mibration across endothelial monolayers is inhibited by anti-PECAM antibodies.The observed alterations in the BBECs could play a role in the development of vasculitis, thrombosis and inflammation that result in blood brain barrier dysfunction and bacterial invasion of the brain parenchyma. These studies involved collaboration with Dr. Corbeil (California) and Dr. K.S. Kim (Johns Hopkins). Objective 3: To develop management and prevention strategies that incorporate new vaccines and treatment protocols to combat bovine respiratory disease and reduce economic loss. Evaluating the effect of vaccinating calves in the face of maternal antibody (IFOMA) on subsequent response to booster vaccination at weaning. The trial to determine whether a multivalent intranasal vaccine (Onset IN) can prime calves vaccinated at 3 days of life or at 60 days of life for an improved response to booster vaccination at weaning is underway. Development of small inhibiting RNA (siRNA) to minimize disease due to BRSV infection. This project is progressing. We recently showed that siRNA directed against the mRNA of the BRSV P gene decreased expression of P mRNA as measured by real time RT-PCR in BRSV infected cells; this confirmed that the siRNA acted as predicted. Initial results in cell culture indicate that siRNA treatment decreased viral replication, as predicted. Assessment of the results and repetition of the studies is underway to confirm that siRNA can suppress BRSV replication. IA had proposed to provide leadership in the development of a modified-live vaccine against Mycoplasma bovis during the project period. Extending its efforts to develop tools to genetically engineer this mycoplasma, mutants with single gene disruptions were studied for resistance to macrophage attack. Wild-type M. bovis strains typically resist macrophages, and this resistance plays a prominent role in the pathogenesis of pneumonia, polyarthritis, and tenosynovitis as caused by the pathogen. Two genes of M. bovis were identified as required to maintain this resistance to macrophage attack. The Genetics of Feedlot Health: South Dakota along with Texas, Illinois, Missouri, New York and Colorado are involved in the Genetics of Feedlot Health Project. This study looks at behavior, genetics, nutrition along with microbiology and immunology on respiratory disease and carcass quality. This 2-year project is in its final year and all the data is still being analyzed.

B.J. White, D.G. Renter. Bayesian estimation of the performance of clinical observations and harvest lung scores for diagnosing bovine respiratory disease in post-weaned beef calves. J Vet Diagn Invest July 2009 Vol. 21, Number 4: 446-453. A. Babcock, B.J. White, D.G. Renter, S.S. Dritz, D.U. Thomson. Feedlot health and performance effects associated with the timing of respiratory disease treatment. J Anim Sci 2009 87:314-227. G.A. Hanzlicek, B.J. White, D. Anderson, D. Mosier, D.G. Renter. Pathological and physiological changes following induced Mannheimia pneumonia in beef feeder calves. Amer J Vet Res. Accepted. B.J. White, G. Hanzlicek, M.W. Sanderson, D.E. Sanderson, R.L. Larson. Prevalence of Mollicutes species in beef feeder calves at arrival and first treatment for bovine respiratory disease. Can Vet J. Accepted. Shen, W. and C. Jones. 2008. Open reading frame 2 encoded by the latency related gene of bovine herpesvirus 1 has anti-apoptosis activity in transiently transfected neuroblastoma cells. J. Virology, 82:10940-10945. Saira, K., S. Chowdhury, N. Gaudreault, L. da Silva, G. Henderson, A. Doster, & C. Jones. 2008. The zinc RING finger of the bovine herpesvirus 1 encoded bICP0 protein is crucial for viral replication and virulence. J. Virology, 82:12060-12068. Brum. M.C.S., C. Coats, B.R. Sangena, A. Doster, C. Jones, and S.I. Chowdhury. 2009. Bovine herpesvirus type 1 (BoHV-1) anterograde neuronal transport from trigeminal ganglia to nose and eye requires glycoprotein E. J. Neurovirology, 15:1-6. Saira, K., Y. Zhou, and C. Jones. 2009. The infected cell protein 0 encoded by bovine herpesvirus 1 (bICP0) associates with interferon regulatory factor 7 (IRF7), and consequently inhibits beta interferon promoter activity. J. Virology. 83:3977-3981. Meyer, F. and C. Jones. 2009. C/EBP-alpha cooperates with bTIF to activate the bovine herpesvirus 1 immediate early transcription unit 1 promoter. J. Neurovirology 15:123-130. Ellis, J., S. Gow, N. Goji, C. Jones, A. Workman, G. Henderson, G. Alaniz, and T. Meinert. Efficacy of a combination viral vaccine in protecting cattle from experimental infection with bovine herpesviruses-1 isolated from recent vaccine breaks. J. of American Veterinary Medical Association, IN PRESS. Workman, A., S. Perez, A. Doster, and C. Jones. 2009. Dexamethasone treatment of calves latently infected with bovine herpesvirus 1 (BHV-1) leads to activation of the bICP0 early promoter, in part by the cellular transcription factor C/EBP-alpha. J. Virology, IN PRESS. Taylor JD, Fulton RW, Dabo SM, Lehenbauer TW, Step DL, Confer AW. Molecular characterization of Pasteurella multocida isolates from fatal cases of bovine respiratory disease. Can Vet J, 2009, in press Taylor JD, Fulton RW, Lehenbauer TW, Step DL, Confer AW. The epidemiology of bovine respiratory disease: What is the evidence for preventive measures? Can Vet J, 2009, in press Confer AW, Ayalew S, Step D L, Trojan B, Montelongo M. Intranasal vaccination of young Holstein calves with Mannheimia haemolytica chimeric protein PlpE-LKT (SAC89) and cholera toxin Vet Immun & Immunopathol, 2009, available online as of May 23, 2009 Singh K, Confer AW, Hope JC, Rizzi T, Wyckoff JW, Weng HY, Ritchey JW. Cytokine mRNA modulation in bovine alveolar macrophages challenged with the wild type and leukotoxin-deficient mutant of Mannheimia haemolytica. Mol Pathog, accepted with revisions, 2009 Ayalew S, Step DL, Montelongo M, Confer AW. Intranasal vaccination of calves with Mannheimia haemolytica chimeric protein containing the major surface epitope of outer membrane lipoprotein PlpE, the neutralizing epitope of leukotoxin, and cholera toxin subunit B. Vet Immun & Immunopathol, In press, 2009. Step, D.L., Krehbiel, C.R., DePra, H.A., Cranston, J.J., Fulton,R.W.,Kirkpatrick,J.A., Gill, D.R., Payton, M.E., Montelongo, M.A., Confer, A.W.: Effects of Commingling Beef Calves from Different Sources and Weaning Protocols During a Forty-Two-Day Receiving Period on Performance and Bovine Respiratory Disease. Journal of Animal Science. 86:1-13, 2008. Step, D.L., Litherland, N.B., Burciaga-Robles, L.O., Breshears, M.A., Krehbiel, C.R., Confer, A.W., Fulton, R.W., Morgan, G.L., Thornsberry, R.M., Fassig, S.M.: Clinical Observations, Biochemical Data, and Postmortem and Histopathologic Findings in Young Dairy Calves Fed Zeolite Clinoptilolite Binder Combined with Milk Replacer. American Journal for Veterinary Research 69: 1587-1594, 2008. Hessman, B.E., Fulton, R.W., Sjeklocha, D.B., Murphy, T.A., Ridpath, J.F., Payton, M.E.: Evaluation of the Economic Effects and the Health and Performance of the General Cattle Population After Exposure to Cattle Persistently Infected with Bovine Viral Diarrhea Virus in a Starter Feedlot. American Journal for Veterinary Research. 70:73-85, 2009. Fulton, R.W., Hessman, B.E., Ridpath, J.F., Johnson, B.J., Burge, L.J., Kapil.S. Braziel, B., Kautz, K., Reck, A.: Multiple Diagnostic Tests to Identify Cattle with Bovine Viral Diarrhea Virus and Duration of Positive Tests in Persistently Infected Cattle. In Press. Canadian Journal for Veterinary Research. 73: 117-124, 2009. Fulton, R.W., Whitley, E.M., Johnson, B.J., Ridpath, J.F., Kapil, S., Burge, L.J., Cook, B.J., Confer, A.W.: Beef Herds in a South Central United States Study: Prevalence of Bovine Viral Diarrhea Virus (BVDV) Persistently Infected Cattle and BVDV Subtypes in Affected Cattle. In press. October 2009. Canadian Journal for Veterinary Research Step, D.L., Krehbiel, C.R.., Burciaga-Robles, LO., Holland, B.P., Fulton,R.W., Confer,A.W., Hutcheson, J., Brister, D., Newcomb,H., Bechtol, D.: A Comparison of Single Vaccination and Revaccination with a Modified Live BHV1-BVDV( type 1 and 2-PI3V-BRSV Vaccine in the Prevention of Bovine Respiratory Disease. Accepted for publication .2009. Journal of American Veterinary Medical Association Ridpath, J.F., Fulton, R.W.: Knowledge Gaps Impacting the Development of BVDV Control Programs in the United States. 2009. Accepted for publication. 2009. Journal of American Veterinary Medical Association. Fulton, R.W., Blood, K.S., Panciera, R.J., Payton, M.E., Ridpath, J.F., Confer, A.W., Saliki, J.T., Burge, L.J., Welsh, R.D., Johnson, B.J., Reck. A.: Lung Pathology and Infectious Agents in Fatal Feedlot Pneumonias and Relationship with Mortality, Disease Onset, and Treatments. Journal of Veterinary Diagnostic Investigation 21: July 2009, in press. Chase CCL, LJ. Braun, P Leslie-Steen, T Graham, D Miskimins JF Ridpath. 2008. Bovine Viral Diarrhea Virus Multi-Organ Infection in Two White-tailed Deer in Southeastern South Dakota. J Wildlife Dis 44:753-759 Ridpath JR, EA Driskell, CCL Chase, JD Neill, MV Palmer, BW Broderson. Reproductive tract disease associated with inoculation of pregnant white-tailed deer with bovine viral diarrhea virus. AJVR 69:1630-1636. Zimmerman AD, RE Buterbaugh, JA Schnackel, CCL Chase. Efficacy of a modified-live virus vaccine administered to calves with maternal antibodies and challenged seven months later with a virulent bovine viral diarrhea type 2 virus. The Bovine Practitioner 43:35-43. Kuckleburg, C. J., D. J. McClenahan, and C. J. Czuprynski. 2008. Platelet activation by Histophilus somni and its LOS induces endothelial cell pro-inflammatory responses and platelet internalization. Shock 29:189-196. Kuckleburg CJ, Tiwari R, Czuprynski CJ. 2008. Endothelial cell apoptosis induced by bacteria-activated platelets requires caspase-8 and -9 and generation of reactive oxygen species. Thromb. Haemost. 99:363-372. McClenahan, D., K. Hellenbrand, D. Atapattu, N. Aulik, D. Carlton, A. Kapur, and C.J. Czuprynski. 2008. Effects of lipopolysaccharide and Mannheimia haemolytica leukotoxin on bovine lung microvascular endothelial cells and alveolar epithelial cells. Clin. Vaccine Immunol. 15:338-347. Atapattu DN, Albrecht RM, McClenahan DJ, Czuprynski CJ. 2008. Dynamin-2-dependent targeting of Mannheimia haemolytica leukotoxin to mitochondrial cyclophilin D in bovine lymphoblastoid cells. Infect Immun. 76:5357-5365. Kisiela DI, Czuprynski CJ.2009. Identification of Mannheimia haemolytica adhesins involved in binding to bovine bronchial epithelial cells. Infect Immun. 2009 77:446-455. McClenahan D, Hillenbrand K, Kapur A, Carlton D, Czuprynski C. 2009. Effects of extracellular ATP on bovine lung endothelial and epithelial cell monolayer morphologies, apoptoses, and permeabilities. Clin Vaccine Immunol. 16:43-48. Atapattu DN, Aulik NA, McCaslin DR, Czuprynski CJ. 2009. Brief heat treatment increases cytotoxicity of Mannheimia haemolytica leukotoxin in an LFA-1 independent manner. Microb Pathog. 46:159-165. Rivera-Rivas JJ, Kisiela D, Czuprynski CJ. 2009. Bovine herpesvirus type 1 infection of bovine bronchial epithelial cells increases neutrophil adhesion and activation. Vet Immunol Immunopathol. Apr 11. [Epub ahead of print]. Tiwari R, Sullivan J, Czuprynski CJ. 2009. PECAM-1 is involved in neutrophil transmigration across Histophilus somni treated bovine brain endothelial cells. Microb Pathog. Jun 12. [Epub ahead of print] Presentations Woolums AR and Chase CCL. New discoveries in cattle health: how your actions influence funding decisions. Proceedings of the 41st Meeting of the American Association of Bovine Practitioners. September 25-27, 2008. Charlotte, NC, p. 205-208. Krunkosky TM, Jarrett CL, Ard MB, Bettis CL, Berghaus LJ, Hurley KAE, Woolums AR. Establishment of Bovine Primary Respiratory Epithelial Cell Cultures From Live Calves and Evaluation of Cell Responses to Bovine Respiratory Syncytial Virus Infection. Proceedings of the 89th Annual Meeting of the Conference for Research Workers in Animal Disease. December 7-9, 2008. Chicago, IL, p. 155. Woolums AR. Practical approaches to vaccination of the calfvaccinating in the face of maternal antibody. 15th American Dairy Science Association Discover Conference on Food Animal Agriculture: Biology of the Calf, Birth to 4 Months. Nov. 16-19, 2008. Roanoke, VA. Woolums AR. The bovine immune response to BRSV infection: helpful or harmful? Western Canadian Association of Bovine Practitioners 18th Annual Conference. January 15-17, 2009. Saskatoon SK, Canada. Woolums AR. Effectively vaccinating calves to prevent respiratory disease. Western Canadian Association of Bovine Practitioners 18th Annual Conference. January 15-17, 2009. Saskatoon SK, Canada. Woolums AR. Feedlot AIP: what the heck causes it? Western Canadian Association of Bovine Practitioners 18th Annual Conference. January 15-17, 2009. Saskatoon SK, Canada. Woolums AR, Krunkosky TM, Jarrett CL, Ard MB, Berghaus LJ, Bettis CL, Hurley KAE. Development of primary bovine bronchial epithelial cell (BBEC) cultures from live calves, and evaluation of cell responses to viral infection. 2009 American College of Veterinary Internal Medicine Annual Forum, June 3-6, 2009, Montreal QC, Canada. Berghaus LJ, Blas-Machado U, Vandenplas ML, Galland KL, Davis CE, Hurley KAE, Woolums AR. Comparison of three methods of identification of nasal BRSV shedding in calves. 5th International Veterinary Vaccines and Diagnostics Conference, July 19-23, Madison, WI, P12. Woolums A, Krunkosky T, Jarrett C, Ard M, Bettis C, Berghaus L, Hurley K, Kyser J. Establishment of bovine primary bronchial epithelial cell cultures from live calves and evaluation of cell responses to bovine respiratory syncytial virus (BRSV) infection. 2009 Bovine Respiratory Disease Symposium, August 5-6, 2009, Colorado Springs, CO, p. 82. Hurley DJ. Role of maternally derived white blood cells passed in the colostrum on immune function. 15th American Dairy Science Association Discover Conference on Food Animal Agriculture: Biology of the Calf, Birth to 4 Months. Nov. 16-19, 2008. Roanoke, VA. Hurley DJ. The transfer of maternal immunity and its impact on calf health and productivity. Academy of Veterinary Consultants Summer Meeting, August 6-8, 2009. Hurley DJ. An overview of the host immune response to bacterial and viral pathogens. Academy of Veterinary Consultants Summer Meeting, August 6-8, 2009. Rosenbusch, R. F., and N. Lee. Polyamine transport as virulence factor in Mycoplasma bovis: role in resistance to attack by macrophages. Poster G-007, 109th General Meeting of the American Society for Microbiology, Philadelphia, PA, 2009. Rosenbusch, R.F., N. Lee, and L. Christensen. Identification of Mycoplasma bovis genes involved in uptake of unopsonized mycoplasmas by activated macrophages. 17th International Organization for Microbiology Congress, Poster 133, Tianjin, China, 2008. Rosenbusch, R.F., N. Lee, D. R. Zamzow, C. D. Riedell, and L. Christensen. Use of a respiratory tract infection model in cattle to screen transposon 4001 mutants of Mycoplasma bovis. 17th International Organization for Microbiology Congress, Presentation in Seminar IV: Molecular and cell biology of mollicutes, Tianjin, China, 2008. Lee, N., D. R. Zamzow, C. D. Riedell, and R. F. Rosenbusch. Development of a transposon 4001 mutant library of a pathogenic Mycoplasma bovis strain. 17th International Organization for Microbiology Congress, Poster 207, Tianjin, China, 2008. Fulton, R.W., Blood, K.S., Panciera, R.J., Payton, M. Ridpath, J.F., Saliki, J.T., Burge, L.J., Confer, A.W., Welsh, R.D., Johnson, B.J., Reck.: Lung Pathology and Infectious Agents in Fatal Feedlot Pneumonias and Relationship with Animal and Treatment Information. American Association of Bovine Practitioners Proceedings. September 25-27, 2008. Charlotte, NC. Taylor, J.D., Fulton, R.W., Lehenbauer, T.W., Dabo, S.M., Confer, A.W.: Molecular Characterization of Pasteurella multocida Isolates from Fatal Feedlot Cases of Bovine Respiratory Disease. American Association of Bovine Practitioners Proceedings. September 25-27, 2008. Charlotte, NC. Ridpath, J.F., Vander Lay, B.L., Sweiger, S.H., Fulton, R.W., Kirkland, P.D.: Prevalence and Antigenic Differences of Bovine Viral Diarrhea Virus Subgenotypes Isolated from Cattle in Australia and the U.S. 51th Annual Meeting of AAVLD, October 22-27, 2008. Greensboro, NC. Fulton, R.W., Eberle, R., Burge, L.J., Reck, A.: Development and Use of Indirect ELISA Tests Detecting Antibodies to Bovine Coronavirus and Bovine Viral Diarrhea Virus in Acute and Convalescent Serums of Cattle. 51th Annual Meeting of AAVLD, October 22-27, 2008. Greensboro, NC. Shelton, T., Hoffman., Fulton.R.W., Ridpath, J.F.: Prevalence of Persistently Infected BVDV Dairy Calves from Dairies with BVDV Vaccination Programs and Distribution of BVDV Subtypes. 4th US BVDV Symposium, January 25-27, 2009. Phoenix, AZ. Fulton, R.W., Ridpath, J.F., Hessman, B.E., Blood, K.S.: Bovine Viral Diarrhea Virus Variability and Prevalence of BVDV Subtypes in Persistently Infected Cattle Entering Feedlots: BVDV1b as Predominant Subtype. 4th US BVDV Symposium, January 25-27, 2009. Phoenix, AZ. Ridpath, J.F., Neil, J., Fulton, R.W., Kirkland, P.D.: Bovine Viral Diarrhea Virus Type Subgenotypes Isolated from Cattle in the U.S. and Australia: Prevalence and Antigenic Differences. 4th US BVDV Symposium, January 25-27, 2009. Phoenix, AZ. Fulton, R.W.: BVD Subtypes: What Matters in the Real World. Western Veterinary Conference. February 17, 2009. Las Vegas, NV. Confer AW, Ayalew S, Montelongo M, Step DL, Wray JH, Hansen RD, Panciera RJ. Immunity of cattle following vaccination of calves with a Mannheimia haemolytica Chimeric PlpE-LKT (SAC89) protein. International Society of Pasteurellaceae Conference, Sorrento, Italy, October 2008. P403 Ayalew S, Confer AW. Immunoproteomic approach to identify and characterize immunologically important Mannheimia haemolytica outer membrane proteins. International Society of Pasteurellaceae Conference, Sorrento, Italy, October 2008. P402 Confer AW. Comparative Pathology of and Pathogenic Mechanisms in Bovine Bacterial Pneumonia. Proceedings, ACVIM, Montreal, June 2009 Confer AW. Immunity against Mannheimia haemolytica: Current knowledge and New Approaches. Proceedings, ACVIM, Montreal, June 2009 Chase CCL, LJ Braun, L Holler, M Spire. Comparing cytopathic and noncytopathic bovine viral diarrhea virus (BVDV) vaccines: antigen trafficking increased to mucosal surfaces with NCP vaccines. 41st annual conference of the American Association of Bovine Practitioners, Charlotte, NC, September 25-27, 2008. Chase CCL, LJ Braun, J Ridpath, R Harland. Comparison of the immune response between a pair of noncytopathic and cytopathic bovine viral diarrhea virus (BVDV) type 1 isolates. 41st annual conference of the American Association of Bovine Practitioners, Charlotte, NC, September 25-27, 2008. Chase CCL, A Young, A Zimmerman, K Gilkerson, K Barling, D Scholz. The induction of a T helper 1 immune response with an inactivated viral vaccine. . 41st annual conference of the American Association of Bovine Practitioners, Charlotte, NC, September 25-27, 2008. Chase C. Bovine viral diarrhea virus persistent infection of white-tailed deer and their risk to domestic cattle. CSREES Awardee Workshop, Chicago, IL, December 7, 2008. Zimmerman AD, RE Buterbaugh, JA Schnakel, CCL Chase. 4th US BVDV Symposium, January 26, 2009, Phoenix AZ. Chase CCL, LJ Braun, L Holler, M Spire. Comparing CP and NCP BVDV vaccines: antigen trafficking increased to mucosal surfaces with NCP vaccines. 4th US BVDV Symposium, January 26, 2009, Phoenix AZ. Chase CCL, A Young, A Zimmerman, K Gilkerson, K Barling, D Scholz. The induction of a T helper 1 immune response with an inactivated viral vaccine. 4th US BVDV Symposium, January 26, 2009, Phoenix AZ. Chase CCL, LJ Braun, J Ridpath, R Harland. Comparison of the immune response between a pair of NCP and CP bovine viral diarrhea (BVDV) type 1 isolates. 4th US BVDV Symposium, January 26, 2009, Phoenix AZ.