HIV Redirecting Innate Immunity by Vpu Targeting of JAK1

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Project Summary/Abstract It is well known that the pathogenesis of HIV is intricately linked to the immune system. For HIV to promote its replication and long-term infection HIV must also modulate cytokine signaling to manipulate the immune microenvironment HIV is existing in. In our previous work we have found that HIV has encoded accessory genes that are able to block the action of the important innate antiviral cytokine named Type I Interferon. Type I Interferons were named for their ability to interfere with the replication of viruses and HIV has encoded multiple ways to block this cytokine. The overall goal of this R03 application is to determine how one of the HIV-encoded genes that blocks Type I Interferon can block this signaling in T cells, the major cell infected by HIV. Long term, this work is critical to set the stage to better understand how HIV sustains itself in a person and avoids elimination by the innate immune system.