Wang Jiangfang, Shackelford Jason M, Casella Carolyn R, Shivers Debra K, Rapaport Eric L, Liu Bindong, Yu Xiao-Fang, Finkel Terri H
Division of Rheumatology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Virology. 2007 Mar 15;359(2):243-52. doi: 10.1016/j.virol.2006.09.026. Epub 2006 Oct 23.
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.
人类免疫缺陷病毒1型（HIV-1）的病毒感染性因子基因（vif）通过使细胞抗病毒因子失活来增加病毒颗粒的感染性，并支持在原代人CD4 T细胞和某些非允许性T细胞系中的有效病毒复制。在此，我们证明Vif也有助于将HIV-1感染的细胞阻滞在细胞周期的G2期。Vif或Vpr缺失的病毒诱导的细胞周期阻滞比野生型病毒少，而同时感染Vif和Vpr均缺失的HIV-1的细胞具有与未感染细胞相当的细胞周期谱。此外，单独的Vif表达诱导细胞在细胞周期的G2期积累。这些数据证明了Vif在细胞周期调控中的新作用，并表明Vif和Vpr在HIV-1感染的细胞中独立驱动G2期阻滞。我们的结果可能对关键HIV-1辅助蛋白在艾滋病发病机制中的作用和相互作用具有启示意义。
