title: Human immunodeficiency virus type 1 Vif causes dysfunction of Cdk1 and CyclinB1: implications for cell cycle arrest.
abstract: The two major cytopathic factors in human immunodeficiency virus type 1 (HIV-1), the accessory proteins viral infectivity factor (Vif) and viral protein R (Vpr), inhibit cell-cycle progression at the G2 phase of the cell cycle. Although Vpr-induced blockade and the associated T-cell death have been well studied, the molecular mechanism of G2 arrest by Vif remains undefined. To elucidate how Vif induces arrest, we infected synchronized Jurkat T-cells and examined the effect of Vif on the activation of Cdk1 and CyclinB1, the chief cell-cycle factors for the G2 to M phase transition. We found that the characteristic dephosphorylation of an inhibitory phosphate on Cdk1 did not occur in infected cells expressing Vif. In addition, the nuclear translocation of Cdk1 and CyclinB1 was disregulated. Finally, Vif-induced cell cycle arrest was correlated with proviral expression of Vif. Taken together, our results suggest that Vif impairs mitotic entry by interfering with Cdk1-CyclinB1 activation.
authors.affiliation: Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Keiko
authors.initials: K
authors.lastname: Sakai
authors.forename: R Anthony
authors.initials: RA
authors.lastname: Barnitz
authors.forename: Benjamin
authors.initials: B
authors.lastname: Chaigne-Delalande
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bidère
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lenardo
mesh_terms: D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002453:Cell Cycle; D056744:Cyclin B1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D019169:Jurkat Cells; D013601:T-Lymphocytes / Q000502:physiology / Q000821:virology; D037521:Virulence Factors / Q000378:metabolism*; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: C534699:CCNB1 protein, human; D056744:Cyclin B1; D037521:Virulence Factors; D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1; D016203:CDC2 Protein Kinase