HIV-1 Vpr increases viral expression by manipulation of the cell cycle:: A mechanism for selection of Vpr in vivo
HIV-1 Vpr increases viral expression by manipulation of the cell cycle:: A mechanism for selection of Vpr in vivo
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DOI：
10.1038/nm0198-065
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发表时间：
1998-01-01
期刊：
影响因子：
82.9
通讯作者：
Emerman, M
中科院分区：
文献类型：
--
作者：
Goh, WC;Rogel, ME;Emerman, M
人类免疫缺陷病毒1型（HIV-1）编码一种名为Vpr的蛋白质，通过阻止受感染细胞进入细胞周期的G（2）期来阻止其增殖。这种Vpr介导的细胞周期停滞在高度分化的猿免疫缺陷病毒中也是保守的，表明在病毒生命周期中起重要作用。然而，目前还不清楚这如何成为病毒的选择性优势。在这里，我们提供的证据表明，病毒基因组的表达是最佳的G（2）期的细胞周期，Vpr增加病毒的生产，通过延迟细胞在细胞周期的长末端重复序列（LTR）是最活跃的点。虽然Vpr是选择对病毒适应组织培养时，我们表明，选择Vpr功能在体内发生在人类和黑猩猩感染HIV-1。这些结果提示了一种新的机制，在快速杀死受感染的靶细胞的情况下，使病毒产量最大化。
The human immunodeficiency virus type 1 (HIV-1) encodes a protein, called Vpr, that prevents proliferation of infected cells by arresting them G(2) of the cell cycle. This Vpr-mediated cell-cycle arrest is also conserved among highly divergent simian immunodeficiency viruses, suggesting an important role in the virus life cycle. However, it has been unclear how this could be a selective advantage for the virus. Here we provide evidence that expression of the viral genome is optimal in the G(2) phase of the cell cycle, and that Vpr increases virus production by delaying cells at the point of the cell cycle where the long terminal repeat (LTR) is most active. Although Vpr is selected against when virus is adapted to tissue culture, we show that selection for Vpr function in vivo occurs in both humans and chimpanzees infected with HIV-1. These results suggest a novel mechanism for maximizing virus production in the face of rapid killing of infected target cells.