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The hypothesis is that PRRSV non-structural protein 1 (Nsp1) and Nsp2 function as immune modulators to decoy the ability of the immune system on focusing protective targets.<P> The objectives for the BARC efforts are to determine the effect of PRRSV Nsp1 and Nsp2 on innate and cell mediated immunity and compare the in vivo properties of viable Nsp2 mutants (infectious clones) with that of parental viruses.
Approach: This project is targeted at understanding the function of the PRRSV non-structural proteins (Nsps) in viral pathogenesis and host immunity. We hypothesize that PRRSV Nsp1 and Nsp2 function as immune modulators to decoy the ability of the immune system on focusing protective targets.<P> Specific objectives are 1). To determine the effect of PRRSV Nsp1 and Nsp2 on innate and cell mediated immunity; 2). To identify the immunoreactive B cell epitopes on Nsp1; 3). To determine whether a specific immunodominant B cell epitope of Nsp1 or Nsp2 can be eliminated from the virus using reverse genetics; 4). To compare the in vivo properties of viable Nsp2 mutants with that of parental viruses. Studies at BARC will be compare tissue and cell immune gene and protein expression responses, asking whether certain cytokines can be more effectively stimulated with different Nsps. <P>These Nsp studies will lead to development of improved PRRS control strategies. The infection and sample collection from pigs, which will be conducted at South Dakota State Univ. Testing for cytokine expression will be conducted at BARC.