Project Summary/Abstract Replication and pathogenesis of any virus within a human host is dependent on how well the virus is able to bypass the many defense systems of the immune system. In particular, Type I Interferons are cytokines that induce the quintessential anti-viral systems within a human. All known viruses that cause disease in humans have systems to circumvent detection and/or action of this potent cytokine. We have sought to determine if and how HIV is able to ?hide? from these systems. We have found that HIV can block both the induction of Type I Interferon as well as the induction of an antiviral state caused by Type I Interferon. We propose to determine how these proteins work to subvert the innate immune response by manipulating the Type I Interferon systems. The significance of these studies will be in creating a more complete understanding of the interaction between HIV and the innate immune system and better understand how to use Type I Interferon in a therapeutic approach to controlling HIV infection. This R15 proposal is a key step in strengthening research opportunities for our laboratory and students that are interested in training in biomedical science research.