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.
| Watanabe, Susan M; Medina, Gisselle N; Eastep, Gunnar N et al. (2018) The matrix domain of the Gag protein from avian sarcoma virus contains a PI(4,5)P2-binding site that targets Gag to the cell periphery. J Biol Chem 293:18841-18853 |
| Medina, Gisselle; Zhang, Yongjun; Tang, Yi et al. (2005) The functionally exchangeable L domains in RSV and HIV-1 Gag direct particle release through pathways linked by Tsg101. Traffic 6:880-94 |
