PORCINE REPRODUCTIVE AND RESPIRATORY SYNDROME VIRUS (PRRSV) CAUSES ACUTE RESPIRATORY DISEASES IN YOUNG PIGLETS AND REPRODUCTIVE FAILURES IN SOWS. PRRS IS ONE OF MAJOR DISEASES THAT HAS A TREMENDOUS ECONOMIC IMPACT TO THE SWINE INDUSTRY WORLDWIDE. IT IS ESTIMATED THAT PRRSV CAUSES APPROXIMATELY $640 MILLION LOSS ANNUALLY TO THE SWINE INDUSTRY IN THE U.S. ALONE.THE PRIMARY OBJECTIVES OF THE PROJECT ARE TO DETERMINE THE ROLE OF HOST'S NATURAL RESTRICTION FACTORS IN PRRSV REPLICATION AND TO UNCOVER THE MECHANISMS BY WHICH THESE RESTRICTION FACTORS LIMIT VIRUS REPLICATION. THE LONG-TERM GOAL IS TO FULLY UNDERSTAND THEIR ROLES IN PRRSV PATHOGENESIS AND IMMUNITY. A BETTER UNDERSTANDING OF THE HOST'S NATURAL RESTRICTION FACTORS IN PRRSV REPLICATION WILL FACILITATE THE DEVELOPMENT OF NOVEL STRATEGIES TO MITIGATE THE IMPACT OF PRRSV TO THE SWINE INDUSTRY THROUGH EITHER RATIONALLY DESIGNED EFFECTIVE VACCINES OR TARGETED GENETIC BREEDING OF PRRSV RESISTANT PIGS. MORE IMPORTANTLY, THE KNOWLEDGE WE LEARNED FROM THE PROPOSED STUDY COULD HAVE BROAD IMPLICATIONS IN THE CONTROL AND PREVENTION OF OTHER SWINE INFECTIOUS DISEASES.