HIV-1 Vif promotes the Gâ‚- 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 Gâ‚‚ phase; however, alteration of other cell-cycle phases has not been reported. We ... show that Vif drives cells out of Gâ‚ and into the S phase. The effect of Vif on the Gâ‚- to-S transition is distinct from its effect on Gâ‚‚, because Gâ‚‚ arrest is Cullin5-dependent, whereas the Gâ‚- 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 Gâ‚- to-S transition. These data suggest that Vif regulates early cell-cycle progression, with implications for infection and latency.
Mesh Terms:
Cell Cycle, Cell Proliferation, Cullin Proteins, Cyclin-Dependent Kinase 9, G1 Phase, Gene Expression Regulation, HIV Infections, HIV-1, HeLa Cells, Humans, Models, Biological, Mutant Proteins, Protein Binding, RNA, Small Interfering, S Phase, Transfection, Virus Latency, vif Gene Products, Human Immunodeficiency Virus
Cell Cycle, Cell Proliferation, Cullin Proteins, Cyclin-Dependent Kinase 9, G1 Phase, Gene Expression Regulation, HIV Infections, HIV-1, HeLa Cells, Humans, Models, Biological, Mutant Proteins, Protein Binding, RNA, Small Interfering, S Phase, Transfection, Virus Latency, vif Gene Products, Human Immunodeficiency Virus
Blood
Date: Jan. 27, 2011
PubMed ID: 21149631
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