Jowett J B, Xie Y M, Chen I S
Departments of Microbiology & Immunology and Medicine, University of California-Los Angeles School of Medicine, Los Angeles, California 90095-1678, USA.
J Virol. 1999 Sep;73(9):7132-7. doi: 10.1128/JVI.73.9.7132-7137.1999.
The human immunodeficiency virus type 1 (HIV-1) Vpr protein induces cell cycle arrest at the border of G(2) and M similar to the arrest caused by agents which damage DNA. We determined whether the presence of Vpr would affect the ability of cells to repair DNA. We developed a shuttle vector system to analyze the effect of Vpr upon the repair of UV-damaged DNA. Our results demonstrated that the presence of Vpr decreased the rate of deletions in this system. Of note, cells arrested in G(2) by other genotoxic agents also increased the frequency of DNA repair of UV-damaged shuttle vectors. We did not observe any direct effect of Vpr upon the rate of double-strand break repair and/or nucleotide excision repair of genomic DNA in cells. Our results suggest a role for HIV-1 Vpr in altering the frequency of DNA repair, a property which may have importance for HIV-1 replication and pathogenesis.
1型人类免疫缺陷病毒(HIV-1)的Vpr蛋白可诱导细胞周期在G2期和M期交界处停滞,类似于由损伤DNA的因子所引起的停滞。我们确定了Vpr的存在是否会影响细胞修复DNA的能力。我们开发了一种穿梭载体系统来分析Vpr对紫外线损伤DNA修复的影响。我们的结果表明,Vpr的存在降低了该系统中缺失的发生率。值得注意的是,被其他基因毒性剂阻滞在G2期的细胞也增加了紫外线损伤穿梭载体的DNA修复频率。我们未观察到Vpr对细胞基因组DNA双链断裂修复和/或核苷酸切除修复速率有任何直接影响。我们的结果提示HIV-1 Vpr在改变DNA修复频率方面具有作用,这一特性可能对HIV-1复制和发病机制具有重要意义。