HIV-1 Vif promotes the G?- to S-phase cell-cycle transition.

ABSTRACT: HIV-1 depends on host-cell resources for replication, access to which may be limited to a particular phase of the cell cycle. The HIV-encoded proteins Vpr (viral protein R) and Vif (viral infectivity factor) arrest cells in the G? phase; however, alteration of other cell-cycle phases has not been reported. We show that Vif drives cells out of G? and into the S phase. The effect of Vif on the G?- to-S transition is distinct from its effect on G?, because G? arrest is Cullin5-dependent, whereas the G?- to-S progression is Cullin5-independent. Using mass spectrometry, we identified 2 novel cellular partners of Vif, Brd4 and Cdk9, both of which are known to regulate cell-cycle progression. We confirmed the interaction of Vif and Cdk9 by immunoprecipitation and Western blot, and showed that small interfering RNAs (siRNAs) specific for Cdk9 inhibit the Vif-mediated G?- to-S transition. These data suggest that Vif regulates early cell-cycle progression, with implications for infection and latency.

SUBMITTER: Wang J 

PROVIDER: S-EPMC3320848 | biostudies-other | 2011 Jan

REPOSITORIES: biostudies-other