Fletcher T M, Brichacek B, Sharova N, Newman M A, Stivahtis G, Sharp P M, Emerman M, Hahn B H, Stevenson M
Department of Medicine, University of Alabama, Birmingham 35294, USA.
EMBO J. 1996 Nov 15;15(22):6155-65.
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/SIV(SM) 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/SIV(SM) virion and reverse transcription complex. Characterizing SIV(SM) 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 G2 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/SIV(SM). This segregation is consistent with the conservation of these genes in HIV-2/SIV(SM) evolution, and underscores the importance of both nuclear transport and cell cycle arrest functions in primate lentivirus biology.
人类免疫缺陷病毒和猿猴免疫缺陷病毒（HIV/SIV）的vpr基因编码的蛋白质会被包装进病毒颗粒中。HIV-1 Vpr已被证明能介导病毒逆转录复合物在非分裂靶细胞（如终末分化的巨噬细胞）中的核输入，并改变被感染宿主细胞的细胞周期和增殖状态。HIV-2/SIV（SM）组的成员除了编码Vpr外，还编码一种名为Vpx的相关蛋白质。由于这两种蛋白质具有相当大的序列相似性，因此人们认为它们也具有相似的功能。在此，我们报告，尽管Vpr和Vpx都是HIV-2/SIV（SM）病毒体和逆转录复合物的组成部分，但它们的功能是不同的且不可相互替代。通过对一个或两个基因有缺陷的SIV（SM）前病毒进行特征分析，我们发现Vpx对于病毒逆转录复合物的核输入既是必需的也是充分的。相比之下，Vpr而非Vpx抑制了被感染宿主细胞从细胞周期的G2期进入M期。因此，HIV-1 Vpr蛋白的两种独立功能由HIV-2/SIV（SM）中的不同基因编码。这种分离与这些基因在HIV-2/SIV（SM）进化中的保守性一致，并强调了核运输和细胞周期停滞功能在灵长类慢病毒生物学中的重要性。
