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Blood. 2011 Jan 27;117(4):1260-9. doi: 10.1182/blood-2010-06-289215. Epub 2010 Dec 13.

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

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  • 1Division of Rheumatology, The Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA.

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 G₂ phase; however, alteration of other cell-cycle phases has not been reported. We show that Vif drives cells out of G₁ and into the S phase. The effect of Vif on the G₁- to-S transition is distinct from its effect on G₂, because G₂ arrest is Cullin5-dependent, whereas the G₁- 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 G₁- to-S transition. These data suggest that Vif regulates early cell-cycle progression, with implications for infection and latency.

PMID:
21149631
[PubMed - indexed for MEDLINE]
PMCID:
PMC3320848
Free PMC Article

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