Gag Protein Interactions Important for HIV Assembly

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DESCRIPTION: The long-term goal of this project is to identify critical virus-host protein interactions of the human immunodeficiency virus type 1 (HIV-l). The gag gene is the only viral gene required for assembly, transport, and release of viral particles but several cellular proteins participate. Our studies suggest that cyclophilin A (CyP A) controls the maturational refolding of Gag to enhance the competence of the viral capsid in the next replicative cycle. Tsg 101, a protein required for trafficking using the endosomal apparatus, may promote efficient viral particle release. We will determine the functional significance of the Tsg 101-Gag interaction in virus replication by identifying the Gag assembly defect in a cell line impaired in tsg1O1 expression (Aim 1). We will determine the role of CyP A by defining the mechanism underlying CyP A control of maturational refolding and the significance of CyP A-induced structural changes for viral infectivity (Aim 2). The third goal is to identify cellular pathways that participate in Gag trafficking and assembly. A combination of molecular genetic, fluorescence microscopy, and protein biochemistry techniques will be used.