Tsg101 and Other Cellular Co‐Factors in HIV Assembly and Release

Abstract

The product of the gag gene of the human immunodeficiency virus type 1 (HIV-1) and other Retroviridae is sufficient for targeting the encoded structural precursor polyprotein (Gag) to assembly sites on the plasma membrane. The interaction of Gag with the cellular protein, Tsg101, facilitates the trafficking and release of viral particles, making Tsg101 a potential target for development of anti-viral agents. Gag binds Tsg101 through a PTAP motif (L domain) in the C-terminal Gagp6 region. Binding is required for efficient Gag release. Tsg101 functions in recognition and sorting of ubiquitin-modified cellular cargo in the endocytic trafficking system. Using a variety of experimental approaches, including proteomics, confocal imaging, molecular genetics and biochemistry, protein constituents that are specifically recruited by the viral L domain were identified. The results suggest that Gag exploits Tsg101 to capture components of endo/exocytic trafficking machinery that facilitate vesicular trafficking within the cell. These studies will assist in evaluation of the feasibility of targeting Tsg101. These studies were supported by NIH grant R01-GM48294 (to CC). GM is a recipient of a W. Burghardt Turner Fellowship.