Brief Summary of Minutes of Annual Meeting

AGENDA: Wednesday September 24; 8:30 am: Welcome; 8:40-10:00 am: Station reports; 10:00-10:15: Break; 10:15 am - 12:00 noon: Station Reports; 12:00 - 1:00 pm: Lunch; 1:00-2:15 PM: Conference call with Gary Sherman and Peter Johnson, CSREES; 2:15-2:45 pm: Discussion of presentation to be made to AABP on the problem of insufficient funding for bovine disease research; 2:45-4:30 pm: Business meeting; 4:30-5:00 pm: Complete station reports; 5:00 pm: Adjourn; Thursday September 25, 2008; 8:00-9:00 am: Open forum for discussion of bovine respiratory disease. MINUTES: September 25, 2008 2:45-4:30 pm: Business meeting. Meeting began at 2:45 pm. Brief discussion of midterm report being written and organized by Ricardo Rosenbusch. Update on National BRD Symposium (to be sponsored by NC-1027 and held August 5 and 6, 2009) presented by Amelia Woolums, chair of organizing committee (organizing committee: Chris Chase, Robert Fulton, Ricardo Rosenbusch). Discussion of BRD session organized by Lynette Corbeil for NC-1027 at CRWAD, Monday December 7, 2008. Plan made for 2009 meeting of Technical Committee to occur on Friday morning August 7, after the BRD Symposium, at the Crown Plaza in Colorado Springs, CO. Chris Chase agreed to serve as President of Technical Committee for 1 more year, and Amelia Woolums will serve as Secretary of Committee for 1 more year. Notes from Teleconference with Dr. Gary Sherman and Dr. Peter Johnson: Committee asked if BRD would remain on the list of fundable diseases for NRI. Dr. Johnson said that he couldnt say for sure, but if BRD is still an important issue, it is likely to stay on list. If stakeholders continue to identify BRD as a problem in routine feedback to USDA CSREES, and particularly at the stakeholder meeting scheduled for 2010, it will be very likely to stay on list. Given that, from year to year things can change regarding priorities for funding. Chuck Czuprynski noted that multistate projects were mentioned as a specific target for funding in the AES call for proposals this year. Committee asked if this indicated some special attention to multistate projects like NC-1027, or was this in reference to something else? Dr. Sherman said that no significant policy changes had been made on how AES funding is distributed; this is still up to the Expt. Station Directors. If special mention was made most likely just reflected local considerations. Drs. Johnson and Sherman outlined upcoming reorganization of CSREES, and the timetable for the RFP for FY 2009. Highlights: NRI is going to become the Agricultural and Food Research Initiative (AFRI) in 2009; this will be announced in Nov. or Dec. 2008. Formation of AFRI is not a cause for concern; in fact, its formation in the new Farm Bill was intended to provide a fresh look at how agricultural research should be done/funded. Big change: NRI could only fund research projects and integrated (combined research/education/extension) projects. AFRI will be able to fund research, integrated, OR solely education or extension projects. Not confirmed that such projects will be solicited, but they could be. Other changes: AFRI is authorized for funding up to $700 million, though actual amount funded will depend on appropriation. NRI had only been authorized for funding up to $500 million (though the largest amount every appropriated was $191 million in 2008). Indirect costs for AFRI funded projects will be capped at 22% (NRI: capped at 20%). AFRI has authority to fund projects for up to 10 years (though this will likely be very rare in practice; NRI had authority to fund projects for up to 5 years). AFRI will have 6 focus areas, the area relevant to animal disease will be Animal Health, Animal Production, and Animal Products (in NRI, the relevant area was Genomics and Biosecurity). Things not changed in AFRI vs NRI: Both basic and applied studies will be funded. Matching requirements will be essentially the same. Postdoc awards, etc. will still be funded. Deadlines for FY 2009: The NRI RFA has not been posted because CSREES has been involved in working toward reorganization. NRI will cease to exist as of this year, thus there will be no RFA for NRI (proposals currently funded under NRI will continue under NRI for now but eventually will be switched to AFRI). All deadlines for proposals to be funded through AFRI will be announced when the description of AFRI and other products of the reorganization of CSREES is announced in Nov or Dec 2008. Dr. Johnson estimates that letters of intent for AFRI will be due in January 2009, and proposals will be due in March 2009. In 2010, AFRI may go back to a fall application deadline, not certain. Change in application process: Because many have noted that the Pure Edge system is cumbersome, its use by Grants.gov is to be discontinued. Proposals will be submitted using pdf files [note: as of now it wasnt clear exactly how this would work]. Other changes: CSREES is being converted into the National Institute for Food and Agriculture (NIFA). The director of NIFA will be a political appointee (but will not require Congressional approval) with a 4 to 6 year term who reports to the Secretary of Agriculture. This is [at least in part] a result of land grant universities wishing for research, extension, and education activities to be more visible to the Secy. of Ag. The current Head of CSREES, Colleen Heffren, is a civil servant. Not sure what will happen to her position. Drs. Johnson and Sherman anticipate that appointing the Director of NIFA may not be the highest priority for the new President, so they will likely operate under an Interim Director until sometime well into 2009 [or perhaps later]. The actual structure of NIFA will be determined by the Director, so for the time being organization will likely change little, but may change much in the future. So this may impact where Dr. Johnson and Dr. Sherman are placed in the NIFA organization. NIFA will have a Chief Scientist who will be under the Director and will be equivalent to an Undersecretary. The Chief Scientist will oversee the Directors of the 6 units of NIFA (which will have the same names as the 6 programs in AFRI, which should make it more clear how activities are administered). Thus, there will be a Director of Animal Health, Animal Production, and Animal Products who will be responsible for programs related to animal disease research, education, and extension. The Chief Scientist will also oversee APHIS and other units formerly included in CSREES. Significant change: USDA ARS and CSREES will be combined in NIFA. This should improve interaction and communication regarding agricultural research funded by USDA. Dr. Johnson pointed out that, funding-wise, BRD fares well in NRI. In the past fiscal year 6 research proposals and 2 conference proposals related to BRD [including NC-1027s BRD Symposium proposal for $10,000] were funded at a total of just over $2.2 million. This represented about 20% of the funds available through the Animal Protection program. The committee asked if the formation of NIFA and AFRI would have any impact on multistate projects. Dr. Sherman said no change was anticipated, though the formula (which directs the funding of projects) could always change. NIFA wont have a budget until late in 2009 and so until then will operate on a continuing resolution. Dr. Johnson pointed out that the 406 Integrated Programs were joined with NRI to form AFRI; since the 406 programs were funded at $45 million in 2008, and NRI was funded at $191 million, this means that the total amount of money available through AFRI should be relatively increased over what was available in NRI. The committee asked about the future of the CAP program. The CAP program has strong support, which suggests that it will probably continue. Within the last year all 3 of the current CAP projects were renewed, suggesting there will be no call for new CAP proposals in 2009. There may be a call for new proposals in 2010. Important note about the 1433 program: Dr. Sherman pointed out that in each of several recent years, the President included no funding for the 1433 program, and each year Congress returned it (this is one of the programs through which Formula Funds are awarded). However, this year the Senate also included $0 for 1433 (proposed funding was $5 million, typical of recent years). The budget still has to go through the House and the Conference Committee, but the fact that the Senate budgeted nothing for this program does not bode well for the program. Moreover, the National Veterinary Medical Services (NVMS) Program (which provides loan forgiveness for new grads working in underserved areas of vet med) was funded by the Senate at $5 million. Dr. Sherman couldnt say for sure, but this suggests that the Senate had the idea to stop funding the 1433 Program and to use the funds instead for the NVMS Program. Will have to stay tuned to see how each of these programs is ultimately funded. Next meeting of NC-1027 Technical Committee: Friday August 7, 2009, at the Crown Plaza Hotel in Colorado Springs, CO (the morning after the BRD Symposium). Members in attendance agreed that we should not plan to do station reports in 2009, but rather use the time to discuss the BRD Symposium and to engage in serious discussion about whether a new NC-1027 project should be submitted when the current project ends, in light of the greatly decreased rate of attendance at the annual meeting in the past 4 years. September 25, 2008 8:00-9:00 am: Open forum for discussion of bovine respiratory disease. Approximately 70 people from AABP Convention were in attendance; these attendees posed questions to members of NC-1027, and shared their experience with BRD, leading to good discussion. Dr. Ricardo Rosenbusch took notes and Dr. Dan Grooms has offered to summarize the notes and will ask Dr. Riddell (AABP Exec. Director) if the notes can be published in the AABP newsletter. Minutes were recorded by Dr. Amelia Woolums.

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. Kansas evaluated the effect of ear-notch sample handling on the reliability of antigen-capture ELISA testing for BVDV. Neither the volume of PBS added to sample, nor time after collection affected the outcome of the assay. A comparison of pooled testing to individual testing of ear-notch samples was also made. Based on test detection limits and economic factors, a pool size of 5-10 notches appeared to be the most advantageous for detecting BVDV. Kansas also explored the use of cardiac troponin level measurements in blood as an indicator to aid in field diagnosis of bovine respiratory disease. An I-STAT 1 hand-held blood analyzer was used to measure Troponin-I in healthy and BRD-affected calves, and affected calves had significantly higher Troponin I levels in blood. Michigan continued the development of a biosensor chip to be used in the detection of BVDV persistently infected cattle. The rapid conductimetric sensors developed to date still lack the sufficient sensitivity for field use. South Dakota reported on diagnostic findings of bovine respiratory bacteria and viruses for 2008. Comparative use of various diagnostic tests for the detection of persistent BVDV were also reported. Wisconsin reported on bacterial and viral diagnostic results from BRD cases. Oklahoma reported on difficulties using a commercial antigen-capture ELISA test for BVDV persistence. The erratic results could be overcome by freezing ear-notch washes before testing. OBJECTIVE 2: To investigate the basic biology, molecular pathogenesis, and immunopathogenesis of polymicrobial infections including important viral and bacterial agents. California examined the in vitro adherence of Histophilus somni on bovine turbinate cells infected with BRSV, and the expression of virulence factors by H. somni under these culture conditions. No significant effect of the viral infection on adherence or expression of virulence factors of H. somni was found, even though concurrent infection of calves with these two agents resulted in increased severity of disease and persistence of H. somni in lung. Georgia reported the successful cultivation of bovine respiratory ciliary epithelial cells. When these cells were infected with BRSV, a transient and elevated mRNA synthesis to the chemokines IL-8 and RANTES, and the adhesion molecule ICAM-1 were detected. Kansas investigated the use of bovine adrenal gland endothelial cell monolayers as a permeability barrier for macromolecules. Substance P and histamine were reported to cause increased permeability across the monolayer, while TNF and LPS did not. Mississippi reported on initial proteogenomic mapping efforts for Mannheimia haemolytica, Pasteurella multocida, and H. somni. Protein profiling was accomplished on bovine monocytes infected with a cytopathic or noncytopathic BVDV virus. Several protein kinases were reduced in expression in monocytes infected with cytopathic BVDV. Nebraska studied the transcriptional activator bICPO of BHV-1. A mutant of the virus with single amino acid changes in the zinc finger domain of b ICPO was shown to grow inefficiently in bovine cells in vitro and calf mucosa in vivo. Other studies focused on the enhancing interaction of host cell transcription factors with viral transcription factors in this model. Studies are on-going on the effect of latency reactivation gene protein of BHV-1. The protein appears to spare neurons from apoptosis induced by exogenous agents. Wisconsin continues to study intracellular pathways that result in leukocyte death following exposure to M. haemolytica leukotoxin. Once internalized, the leukotoxin is transported to the mitochondria. This transport is correlated with actin filament formation and dynamin relocation from mitochondria to the cell membrane. Bovine pulmonary epithelial cells were compared to endothelial cells in their response to LPS. Endothelial cells were shown to be more responsive to LPS, resulting in increased transepithelial resistance, expression of inflammatory cytokines and apoptosis. Epithelial cells only responded with increased inflammatory cytokines. BHV-1 infection of bovine bronchiolar epithelium cell lines resulted in increased adherence of M. haemolytica to these cells. This adherence is mediated by two outer membrane proteins of the bacteria. Wisconsin also continued studies on expression of surface molecules by brain microvascular endothelial cells infected with H. somni. OBJECTIVE 3: To develop management and prevention strategies that incorporate new vaccines and treatment protocols to combat bovine respiratory disease and reduce economic loss. California investigated the use of recombinant GST fusion products of 3 surface immunoglobulin-binding proteins of H. somni. One of the surface proteins, IbpADR2 was shown to be protective for calves challenged after vaccination. The protective effect consisted of lowered clinical scores and lung lesion scores at necropsy. Protection was associated with specific IgG1 and IgG2 with low IgE responses. Iowa developed plasmids carrying the oriC region of Mycoplasma bovis. The plasmids were shown to replicate independently when introduced into M. bovis under antibiotic pressure, and could be removed by releasing the mycoplasma from antibiotic pressure during growth. This genetic tool is critically needed for the development of a modified live M. bovis vaccine. A saturation library of transposon mutants was developed from a virulent M. bovis strain. The mutants are used on ongoing studies to develop a modified live vaccine. Kansas studied weekly incidence of BRD morbidity risk in pens of feedlot cattle. They confirmed that mixed gender groups, multiple source groups, cattle that were shipped for long distances, and light weight calves were at increased risk of morbidity. A study comparing day one methaphilactic use of tulathromycin versus tilmicosin showed that the calves given the longer acting tulathromycin treatment had better health and performance parameters. Michigan has started a regional (upper Michigan peninsula) voluntary eradication campaign. Initial response and participation in the study has been very positive. South Dakota studied the impact of selenium and vitamin E supplementation on antibody response to BHV-1 vaccination and ovalbumin immunization of day-old dairy calves. Organic selenium administration improved overall immune responses of the calves. Wisconsin continued studies on the relationship between air quality, other environmental risk factors and dairy calf respiratory health.

JOURNAL PUBLICATIONS:- Gershwin LJ, Gunther RA, Hornof WJ, Larson RF. Effect of infection with bovine respiratory syncytial virus on pulmonary clearance of an inhaled antigen in calves. Am J Vet Res 3:416-422, 2008. Geertsema RS, Worby C, Kruger RP, Tagawa Y, Russo R, Herdman DS, Lo K, Kimball RA, Dixon J, Corbeil LB. Protection of mice against H. somni septicemia by vaccination with recombinant immunoglobulin binding protein subunits. Vaccine 35:4506-4512, 2008. Reber AJ, Donovan DC, Gabbard J, Galland K, Aceves-Avila M, Holbert KA, Marshall L, Hurley DJ. Transfer of maternal colostral leukocytes promotes development of the neonatal immune system. II. Effects on neonatal lymphocytes. Vet. Immunol Immunopath 123:305-313, 2008. Reber AJ, Donovan DC, Gabbard J, Galland K, Aceves-Avila M, Holbert KA, Marshall L, Hurley DJ. Transfer of maternal colostral leukocytes promotes development of the neonatal immune system. II. Effects on monocyte lineage cells. Vet Immunol Immunopath 123:186-196, 2008. Chase CCL, Hurley DJ, Reber AJ. Neonatal immune development in the calf and its impact on vaccine response. Vet Clin North Am Food Anim Pract 24:87-104, 2008. Funk RA, Thomson DU, Renter DG, White BJ, Guillosou S. Comparison of pooled testing to individual testing with an ear-notch antigen capture ELISA testing for bovine viral diarrhea virus. Bovine Practitioner 42:93-97, 2008. Funk RA, Thomson DU, White BJ, Renter DG, Rust RR. Effects of ear-notch sample handling on reliability of antigen-capture ELISA attesting for BVDV. Bovine Practitioner 42:45-49, 2008. Nickell JS, White BJ, Larson RL, Blasi DA, Renter DG. Comparison of short term health and performance effects related to prophylactic administration of either tulathromycin or tilmicosin to beef stocker calves. Vet Therapeut 9:147-156, 2008. Sanderson MW, Dargatz DA, Wagner BA. Risk factors for initial respiratory disease morbidity counts in US feedlots. Canad Vet J 49:373-378, 2008. Muhammad-Tahir Z, Alocilja EC, Grooms DL. Indium tin oxide polyaniline biosensor: fabrication and characterization. Sensors 7:1123-11490, 2007. Jin JH, Zhang D, Alocilja EC, Grooms DL. Label-0free DNA sensor on nano-porous silicon-polypyrrole chip for monitoring Salmonella species. IEEE Sensors J 8:891-8954, 2008. Nanduri B, Lawrence ML, Peddinti DS, Burgess SC. Effects of sub-minimum inhibitory concentrations of antibiotics on the Pasteurella multocida proteome: a systems approach. Comparative ands Functional Genomics e-pub 254836, 2008. Pinchuk GV Lee S-R, Nanduri B, Honsiger KL, Stokes JV, Pinchuk LM. BVDV differentially alter the expression of the protein kinases and related proteins affecting the development of infection and anti-viral mechanisms in bovine monocytes. Biochim Biophys Acta 1784: 1234-1247, 2008. Lee S-R, Pharr GT, Boyd BL, Pinchuk LM. BVDV modulate toll-like receptors, cytokines and co-stimulatory molecule gene expression in bovine PBMC. Comp Immun Microbiol Infect Dis 31:403-418, 2008. Perez S, Meyer F, Saira K, Doster A, Jones C. Premature expression of the latency related (LR) RNA correlates with higher levels of beta-interferon RNA expression in productively infected cells. J Gen Virol 89:1338-1345, 2008. Geiser V, Rose S, Jones C. BHV-1 induces cell death by a cell type dependent fashion. Microb Pathogen 44:459-466, 2008. Liu ZF, Brum MCS, Doster A, Jones C, Chowdhury SI. A BHV-1 mutant virus specifying a carboxyl terminal truncation of glycoprotein E is defective in anterograde neuronal transport in rabbits and calves. J Virol 82:7432-7442, 2008. Brum MCS, Coats C, Sangena BR, Doster A, Jones C, Chowdhury SI. BHV-1 anterograde neuronal transport from trigeminal ganglia to nose and eye requires glycoprotein E. In Press, J Neurovirol. Zimmerman AD, Butterbaugh RE, Herbert JM, Haas JM, Frank NE, Luempert LG, Chase CCL. Efficacy of BHV-1 inactivated vaccine against abortion and stillbirth in pregnant heifers. JAVMA 231:1386-1389, 2007. Ridpath JF, Mark CS, Chase CCL, Ridpath AC, Neill JD. Febrile response and decrease in circulating lymphocytes following acute infection in white tail deer fawns with either BVDV1 or a BVDV2 strain. J Wildlife Dis 43:653-659, 2007. Atapattu DN, Czuprynski CJ. Mannheimina haemolytica leukotocxin binds to lipid rafts of bovine lymphoblastoid cells (BL-3) and is internalized in a dynamin-2 and clathrin-dependent manner. Infect Immun 75:4719-4725. Behling-Kelly E, McClenahan D, Kim KS, Czuprynski. Viable Haemophilus somnus induce myosin light chain kinase-dependent decrease in brain endothelial cell monolayer resistance. Infect Immun 75:4572-4581. Behling-Kelly E, Kim KS, Czuprynski CJ. Haemophilus somnus activation of brain endothelial cells: potential role for local cytokine production and thrombosis in CNS infection. Thromb Haemostas 98:823-830, 2007. Kuckleburg CJ, McClenahan DJ, Czuprynski CJ. Platelet activation by Histophilus somni and its LOS induces endothelial cell pro-inflammatory cytoikine responses and platelet internalization. Shock 29:189-196, 2008. Kuckleburg CJ, Tiwari R, Czuprynski CJ. Endothelial cell apoptosis induced by bacteria-activated platelets requires caspase-8 and -9 and generation of reactive oxygen species. Thromb Haemost 99:363-372, 2008. McClenahan D, Hellebrand K, Atapattu D, Aulik N, Carlton S, Kapuir A, Czuprynski CJ. Effects of LPS and Mannheimina haemolytica leukotoxin on bovine lung microvascular endothelial cells and alveolar epithelial cells. Clin Vaccine Immunol 15:338-347, 2008. REVIEWS AND BOOK CHAPTERS:- Jones C, Chowdhury SI. A review of the biology of BHV-1. Its role as a cofactor in the BRD complex, and development of improved vaccines. Adv An Health 8:187-205, 2008. Behling-Kelly E, Czuprynski CJ. Endothelial cells as active participants in veterinary infections and inflammatory disorders. Anim. Health Res Rev 8:47-58, 2007. Rosenbusch, R. F. Chapter 43: Mycoplasmas in bovine respiratory disease. In Current Veterinary Therapy Food Animal Practice Vol. 5, D. E. Anderson and D. M. Rings, eds., Saunders, St. Louis, 2009. ABSTRACTS AND CONFERENCE PROCEEDINGS:- Haase C, Quesada M, Mukhtar E, Sharp P, Larson LJ, Thomas C, Schultz RD. Comparative study of three major modified live bovine vaccines for BVDV, BHV-1, PI-3, BRSV, and 5 Leptospira serovars. 88th CRWAD meeting, Dec 2-4, 2007, Chicago. IL. Reber AJ, Donovan DC, Gabbard J, Gallanfd K, Aceves-Avila M, Holbert KA, Marshall L, Hurley DJ. Transfer of maternal colostral leukocytres promotes development of neonatal lymphocytes. 88th CRWAD meeting, Dec 2-4, 2007, Chicago. IL. Woolums AR. Vaccination of calves  New information on the effects of maternal antibody. 40th AABP convention, Sep 20, 2007, Vancouver, BC. Rosenbusch RF, Lee N, Christensen L. Identification of Mycoplasma bovis genes involved in uptake of unopsonized mycoplasmas by activated macrophages. 17th International Organization for Microbiology Congress, Tianjin, China, 2008. Rosenbusch RF, Lee N, Zamzow DR, Riedell CR, Christensen L. Use of a respiratory tract infection model in cattle to screen transposon 4001 mutants of Mycoplasma bovis. 17th International Organization for Microbiology Congress, Tianjin, China, 2008. Lee N, Zamzow DR, Riedell, CR, Rosenbusch RF. Development of a transposon 4001 mutant library of a pathogenic Mycoplasma bovis strain. 17th International Organization for Microbiology Congress, Tianjin, China, 2008. Rosenbusch RF, Zamzow DR, Riedell CD, Lee. N Construction of a random mutant library of Mycoplasma bovis. 108th General Meeting of the American Society for Microbiology, Boston, 2008. Lee N, Zamzow DR, Rosenbusch RF. Identification of the origin of replication in the chromosome of Mycoplasma bovis and its use to construct a replicative plasmid. 108th General Meeting of the American Society for Microbiology, Boston, 2008. Berghaus LJ, Vandenplas ML, Galland KL, Davis CE, Hurley KAE, Blas-Machado U, Woolums AR. Comparison of 3 methods of identification of nasa; BRSV shedding by calves. 88th CRWAD meeting, Dec 2-4, 2007, Chicago. IL. Woolums AR. The problem of insufficient funding for cattle health research. Presented to the AABP Board of Governors Annual Meeting, March 2008. Woolums AR. Immune development in the neonatal calf. Minnesota Nutrition satellite conference, Sep 16, 2008, Owatonna, MN. OTHER (M.S. Thesis):- Rivera, Jose. Effects of BHV-1 infection on bovine neutrophil adhesion to bronchial epithelial cells in vitro. MS thesis, Madison, WI.