2007 Annual Report 1a.Objectives (from AD-416) The goals of this project are to improve the industry's ability to detect and control viral infections of ruminants (principally cattle), with an emphasis of bovine viral diarrhea viruses (BVDV). Detection will be improved by the generation of robust field-ready tests that both detect and differentiate viral pathogens. Limiting and controlling viral infections will require research efforts to generate a more thorough understanding of viral/host interactions and identifying the mechanism(s) behind viral pathogenesis. This project has three objectives: Obj. 1. Develop innovative methods to detect infection in individual animals and to conduct surveillance of animal populations for endemic viral pathogens Obj. 2. Elucidate mechanisms involved in the development of and identify means to detect prolonged and persistent viral infections. Obj. 3. Develop tools to measure and means to limit impact of ruminant infection with viral pathogens. 1b.Approach (from AD-416) This project focuses on filling knowledge and technology gaps that hamper the detection and control of bovine viral diarrhea viruses (BVDV). Reduction of BVDV infections in the national herd requires effective surveillance programs, efficacious vaccines, and reliable means to detect both persistent and acute infections. As the BVDV control program progresses, there will be a need to differentiate between natural exposure and vaccination. Knowledge gaps to be addressed include: basic information regarding BVDV infection in wild cervids; the nature of the immunological, cellular and physiological changes accompanying the development of persistent infections; and the responsiveness of the neonate to vaccination. In addition, surveillance for newly arising BVDV variations will be maintained. Technology gaps will be addressed by: assessing new diagnostic readout methods; examining possible methods for detection of persistently infected animals in utero; and exploring marker vaccine development. Approaches to achieve these goals are to: examine the use of atomic force microscopy and Raman spectroscopy as readout methods; characterize BVDV infections in fawns and pregnant white tail deer; work with a network of laboratories to identify and characterize variant BVDV; compare fetal and associated maternal tissues from normal and persistently infected fetuses; evaluate the use of an infectious clone as a marker vaccine; and characterize the immune responses of neonates to vaccination. Some techniques to be used include phylogenetic analysis, comparative pathogenesis, genetic engineering, and serial analysis of gene expression (SAGE). 4.Accomplishments Title: Improved challenge model for determining efficacy of vaccines against BVDV1 strains Problem: The current challenge model, available from APHIS, for determining efficacy of vaccines in preventing clinical disease following acute infection with BVDV1 strains uses a challenge strain that does not reliably cause clear cut clinical symptoms. Failure to cause clear cut clinical symptoms makes it difficult to interpret efficacy tests. Activity: Field strains from the BVDV1 genotype were isolated and characterized. Cattle were infected with selected field strains under controlled conditions. Severity and reproducibility of clinical symptoms were compared to clinical symptoms observed with the challenge strain currently available from APHIS. Based on these studies a better challenge strain was selected. Impact: Study results and strains were made available to the Center for Veterinary Biologics (CVB). Personnel at CVB are now generating standard operating procedures that use the challenge strain selected in our studies. Use of this better challenge model will yield more reliable information on vaccine efficacy and contribute to BVDV control measures. Title: Characterized BVDV infections in white tail deer Problem: Free-ranging white tail deer populations are frequently in contact with domestic cattle in the U.S. and this enables possible transfer of BVDV between cattle and deer with significant implications for proposed BVDV control programs. The purpose of this study was 2-fold:. 1)to determine if BVDV causes clinical disease in deer similar to the clinical disease it causes in cattle, and. 2)determine if methods used to detect BVDV infection in cattle are adequate to detect BVDV infection in deer. Activity: Fawns and pregnant white tail does, free of BVDV and antibodies against BVDV, were infected with two different strains of BVDV under controlled conditions. Acute and persistent infections with BVDV were observed following inoculation. Tests used to detect BVDV infections in cattle were successful in detecting BVDV infection in white tail deer. Impact: Control programs can use tests, designed for surveillance for BVDV infection in cattle, in evaluating BVDV status of white tail deer herds in contact with cattle. Surveillance of wildlife populations for BVDV infections is important to the design and implementation of BVDV control programs. The accomplishments address National Program 103 – Animal Health Action Plan Component 5: Countermeasures to Prevent and Control Reproductive and Neonatal Diseases 5.Significant Activities that Support Special Target Populations None. 6.Technology Transfer Number of new CRADAs and MTAs 2 Number of active CRADAs and MTAs 2 Number of invention disclosures submitted 3 Number of new commercial licenses granted 1 Number of non-peer reviewed presentations and proceedings 6 Number of newspaper articles and other presentations for non-science audiences 2 Review Publications Driskell, E.A., Ridpath, J.F. 2006. A survey of bovine viral diarrhea virus testing in diagnostic labs in the United States from 2004 to 2005. Journal of Veterinary Diagnostic Investigation. 18(6):600-605. Bendfeldt, S., Ridpath, J.F., Neill, J.D. 2007. Activation of cell signaling pathways is dependant on the biotype of bovine viral diarrhea virus type 2. Virus Research. 126(1-2):96-105.