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pubmed:abstractText |
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.
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pubmed:affiliation |
Division of Rheumatology, The Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA.
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