The Vif accessory protein alters the cell cycle of human immunodeficiency virus type 1 infected cells.
The viral infectivity factor gene (vif) of HIV-1 increases the infectivity of viral particles by inactivation of cellular anti-viral factors, and supports productive viral replication in primary human CD4 T cells and in certain non-permissive T cell lines. Here, we demonstrate that Vif also contributes to the arrest of HIV-1 infected cells in the G(2) phase of the cell cycle. Viruses deleted in Vif or Vpr induce less cell cycle arrest than wild-type virus, while cells infected with HIV-1 deleted in both Vif and Vpr have a cell cycle profile equivalent to that of uninfected cells. Furthermore, expression of Vif alone induces accumulation of cells in the G(2) phase of the cell cycle. These data demonstrate a novel role for Vif in cell cycle regulation and suggest that Vif and Vpr independently drive G(2) arrest in HIV-1 infected cells. Our results may have implications for the actions and interactions of key HIV-1 accessory proteins in AIDS pathogenesis.
Wang
Jiangfang
J
Division of Rheumatology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Shackelford
Jason M
JM
Casella
Carolyn R
CR
Shivers
Debra K
DK
Rapaport
Eric L
EL
Liu
Bindong
B
Yu
Xiao-Fang
XF
Finkel
Terri H
TH
D002453:Cell Cycle; D002478:Cells, Cultured; D015967:Gene Expression Regulation, Viral; D016346:Gene Products, vif / Q000235:genetics / Q000378:metabolism*; D016336:Gene Products, vpr / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D009154:Mutation; D013601:T-Lymphocytes / Q000166:cytology* / Q000502:physiology / Q000821:virology*; D054320:vif Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016346:Gene Products, vif; D016336:Gene Products, vpr; D054320:vif Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus