title: HIV-1 Vif promotes the G₁- 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 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.
authors.affiliation: Division of Rheumatology, The Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA.
authors.forename: Jiangfang
authors.initials: J
authors.lastname: Wang
authors.forename: Emma L
authors.initials: EL
authors.lastname: Reuschel
authors.forename: Jason M
authors.initials: JM
authors.lastname: Shackelford
authors.forename: Lauren
authors.initials: L
authors.lastname: Jeang
authors.forename: Debra K
authors.initials: DK
authors.lastname: Shivers
authors.forename: J Alan
authors.initials: JA
authors.lastname: Diehl
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Yu
authors.forename: Terri H
authors.initials: TH
authors.lastname: Finkel
mesh_terms: D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D042863:Cyclin-Dependent Kinase 9 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D016196:S Phase / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D014162:Transfection; D017735:Virus Latency / Q000187:drug effects / Q000235:genetics; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: C496871:CUL5 protein, human; D044842:Cullin Proteins; D050505:Mutant Proteins; D034741:RNA, Small Interfering; D054320:vif Gene Products, Human Immunodeficiency Virus; C467969:CDK9 protein, human; D042863:Cyclin-Dependent Kinase 9