HIV-1 Vif promotes the G1- to S-phase cell-cycle transition

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(2) phase; however, alteration of other cell-cycle phases has not been reported. We show that Vif drives cells out of G(1) and into the S phase. The effect of Vif on the G(1)-to-S transition is distinct from its effect on G(2), because G(2) arrest is Cullin5-dependent, whereas the G(1)-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(1)-to-S transition. These data suggest that Vif regulates early cell-cycle progression, with implications for infection and latency. (Blood. 2011;117(4):1260-1269)