11th Conference on Retroviruses and Opportunistic Infections San Francisco, California - February 8 - 11, 2004

Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th:Abstract No. 6

Wesley I Sundquist
Eccles Inst of Human Genetics, Univ of Utah, Salt Lake City, USA

BACKGROUND: HIV Gag is a multifunctional protein that coordinates viral trafficking, membrane binding, assembly, co-factor packaging, budding, and maturation. Late in the infectious cycle, Gag is translated in the cytoplasm and transported to plasma and endosomal membranes where it assembles into enveloped particles. In this process, Gag must recruit cellular machinery to enable the assembling particles to bud through the membrane. Previous work has shown that HIV budding requires both the covalent transfer of ubiquitin and the presence of a conserved tetrapeptide motif (PTAP) within the p6 domain of Gag.

RESULTS: We have shown that the cellular protein, TSG101, binds to both ubiquitin and the PTAP motif of the HIV-1 p6 protein and facilitates virus release. TSG101 normally helps to sort ubiquitylated protein cargos into vesicles that bud into late endosomal compartments called multivesicular bodies (MVB). We have recently defined the protein network required for human MVB biogenesis, and demonstrated that the entire pathway is required for HIV release.

CONCLUSIONS: Thus, HIV release and MVB biogenesis appear to be analogous processes. I will discuss our ongoing biochemical and structural studies of protein complexes along the MVB pathway and the generality of this pathway for virus release.

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Copyright © 2004 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.