Project Number: 1245-32000-098-00
Project Type: Appropriated

Start Date: Oct 31, 2011
End Date: Oct 30, 2016

Objective:
Objective 1: Identify genetic variations associated with disease resistance to PRRS virus and identify biological determinants associated with anti-PRRS virus host responses to discover genetic and biological determinants associated with disease resistance to infectious diseases of swine. Objective 2: Discover effective immune intervention strategies to prevent and control infectious diseases of swine by developing immunologic tools to enhance our understanding of swine immune system development and novel assays to evaluate pig responses to infectious diseases; and by assessing differential responses to infection versus vaccination to determine what pathways are associated with protective responses of pigs to respiratory pathogens.

Approach:
Assess whether genomic variation in pigs is associated with differential PRRS resistance/susceptibility and biologic responses to PRRSV infection. The PRRS Host Genetics Consortium (PHGC) was developed to assess the genomic basis of PRRS disease resistance. The PHGC is a national effort to assess pig resistance/susceptibility to primary PRRSV infection and associated growth effects. Our research will focus on the PHGC objectives: 1) use genotyping and phenotyping tools to determine if there are host genes that control resistance/susceptibility to PRRSV infection; 2) verify genetic variation in response to PRRSV, via improved health, survivability and growth; and 3) identify relative importance of different phenotypes, and their heritability, that predict response to PRRSV infection. Identify biological determinants associated with anti-PRRS virus host responses. We hypothesize that there will be functional genomic and proteomic differences that correlate with resistance to PRRSV infections. Using PHGC samples, functional analyses will be performed to identify gene networks and resistance associated biomarkers that differ in high versus low viral load pigs. Our goal would be to identify markers expressed pre-infection, e.g., serum biomarkers in uninfected pigs. Develop immunologic tools to enhance our understanding of swine immune system development and novel assays to evaluate pig responses to infectious diseases. A portion of the time devoted to this project will involve research to develop and improve immune reagents available to characterize swine immune responses and regulation. Numerous commercial sources provide reagents for swine immunity research; yet, compared to human and mouse, these resources are limited. Working with the U.S. Veterinary Immune Reagent Network (VIRN) we will develop new immunologic reagents and assays to measure swine cytokines, chemokines, and immune cell surface molecules. These will help identify key features of an effective swine immune response to infectious pathogens Assess differential responses to infection versus vaccination to determine what pathways are associated with protective responses of pigs to respiratory pathogens. Biomarkers are present in pigs that correlate with protective immunity to respiratory pathogens. Determining whether a response to infection or vaccination is protective or pathologic is essential for the design of new vaccines, diagnostics and therapeutics. For pigs this means understanding the genes and proteins, networks and pathways involved in these responses. Based on the newly finished swine genome sequence, we will identify and annotate some of the numerous genes and regulatory sequences encoded in the swine genome. With that information, functional genomic tools will be applied to assess infection or vaccination responses. Research targets will be infection and vaccination of pigs with respiratory pathogens, particularly PCV2b and PRRSV.