Nuclear import and cell cycle arrest functions of the HIV-1 Vpr protein are encoded by two separate genes in HIV-2/SIVSM
Nuclear import and cell cycle arrest functions of the HIV-1 Vpr protein are encoded by two separate genes in HIV-2/SIVSM
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DOI：
10.1002/j.1460-2075.1996.tb01003.x
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发表时间：
1996-11-15
期刊：
影响因子：
11.4
通讯作者：
Stevenson, M
中科院分区：
文献类型：
--
作者：
Fletcher, TM;Brichacek, B;Stevenson, M
人类和猿猴免疫缺陷病毒 (HIV/SIV) 的 vpr 基因编码包装在病毒颗粒中的蛋白质，HIV-1 Vpr 已被证明可以介导非分裂靶细胞（例如终末分化巨噬细胞）中病毒逆转录复合物的核输入，并改变受感染宿主细胞的细胞周期和增殖状态。除了 Vpr 之外，HIV-2/SIVSM 组的成员还编码一种称为 Vpx 的相关蛋白，因为这两种蛋白具有相当大的序列相似性，因此假设它们也表现出相似的功能。在这里，我们报道 Vpr 和 Vpx 的功能是不同的且非冗余的，尽管这两种蛋白都是 HIV-2/SIVSM 病毒粒子和逆转录复合物的组成部分。表征在一个或两个基因中有缺陷的 SIVSM 原病毒，我们发现 Vpx 对于病毒逆转录复合物的核输入。相反，Vpr而非Vpx抑制受感染宿主细胞从细胞周期的G(2)期进展到M期。因此，HIV-1 Vpr 蛋白的两个独立功能是由 HIV-2/SIVSM 中不同的基因编码的。这种分离与 HIV-2/SIVSM 进化中这些基因的保守性一致，并强调了核运输和细胞周期阻滞功能在灵长类慢病毒生物学中的重要性。
The vpr genes of human and simian immunodeficiency viruses (HIV/SIV) encode proteins which are packaged in the virus particle, HIV-1 Vpr has been shown to mediate the nuclear import of viral reverse transcription complexes in non-dividing target cells (e.g. terminally differentiated macrophages), and to alter the cell cycle and proliferation status of the infected host cell. Members of the HIV-2/SIVSM group encode, in addition to Vpr, a related protein called Vpx, Because these two proteins share considerable sequence similarity, it has been assumed that they also exhibit similar functions, Here, we report that the functions of Vpr and Vpx are distinct and non-redundant, although both proteins are components of the HIV-2/SIVSM virion and reverse transcription complex, Characterizing SIVSM proviruses defective in one or both genes, we found that Vpx is both necessary and sufficient for the nuclear import of the viral reverse transcription complex. In contrast, Vpr, but not Vpx, inhibited the progression of infected host cells from the G(2) to the M phase of the cell cycle. Thus, two independent functions of the HIV-1 Vpr protein are encoded by separate genes in HIV-2/SIVSM. This segregation is consistent with the conservation of these genes in HIV-2/SIVSM evolution, and underscores the importance of both nuclear transport and cell cycle arrest functions in primate lentivirus biology.