Factors Involved in HIV Release and Infectivity

Venue: Edificio Povo 2, via Sommarive nr. 9, Povo (TN)
at 2.00 p.m.

• Heinrich G. Göttlinger, Program in Gene Function and Expression, and Program in Molecular Medicine, University of Massachusetts Medical School, MA 01605

The detachment of progeny HIV-1 virions from the cell surface depends on the cellular ESCRT membrane fission machinery. HIV-1 directly recruits ERSCRT components Tsg101 and ALIX via L domains in HIV-1 Gag. Our results show that Tsg101 becomes dispensable for HIV-1 budding if ALIX is expressed at sufficiently high levels. Furthermore, we have found that Tsg101 can be functionally replaced by an E3 ubiquitin ligase that catalyzes K63-linked ubiquitin chains. Tsg101 and ALIX ultimately engage CHMP4/ESCRT-III, and we have recently identified a novel regulator of CHMP4/ESCRT-III that determines how much is available to catalyze HIV-1 release. The infectivity of released progeny virions depends on the accessory HIV protein Nef, and our results suggest that Nef counteracts a restriction factor that targets HIV-1Env.