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

Conf Retrovir Opportunistic Infect 2004 Feb 8-11; 11:(abstract no. 64)

Strack B, Calistri A, Popova E, Craig S, Gottlinger H; Dana-Farber Cancer Inst., Boston, MA, USA

BACKGROUND: HIV-1 budding requires a membrane fission event to release the nascent virion. This membrane fission event is promoted by the p6 domain of Gag, which recruits Tsg101, a component of the class E vacuolar protein sorting (Vps) machinery. We find that HIV-1 p6 contains a second region involved in budding that interacts with the class E Vps protein AIP1.

METHODS: We used protein microsequencing, GST pull-down, yeast 2-hybrid, and co-immunoprecipitation assays to identify AIP1 as a host protein that interacts with HIV-1 and SIV p6, as well as with other class E Vps proteins.

RESULTS: AIP1 interacts with a conserved C-terminal region of HIV-1 p6 that is critical for viral budding in a minimal Gag context. AIP1 also interacts with Tsg101 and with components of ESCRT-III, a complex required for the budding of cellular vesicles into late endosomes. Dominant-negative versions of AIP1 and of ESCRT-III components potently arrest HIV-1 budding at the cell surface. Our results also indicate that the ESCRT machinery is tightly regulated via autoinhibitory interactions.

CONCLUSIONS: Our results identify AIP1 as a component of the HIV-1 budding machinery that couples HIV-1 p6 to the late-acting endosomal sorting complex ESCRT-III.

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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.