NUCLEAR IMPORT AND CELL-CYCLE ARREST FUNCTIONS OF THE HIV-1 VPR PROTEIN ARE ENCODED BY 2 SEPARATE GENES IN HIV-2 SIVSM/

The vpr genes of human and simian immunodeficiency viruses (HIV/SIV) e ncode proteins which are packaged in the virus particle, HIV-1 Vpr has been shown to mediate the nuclear import of viral reverse transcripti on complexes in non-dividing target cells (e.g. terminally differentia ted macrophages), and to alter the cell cycle and proliferation status of the infected host cell. Members of the HIV-2/SIVSM group encode, i n addition to Vpr, a related protein called Vpx, Because these two pro teins share considerable sequence similarity, it has been assumed that they also exhibit similar functions, Here, we report that the functio ns of Vpr and Vpx are distinct and non-redundant, although both protei ns are components of the HIV-2/SIVSM virion and reverse transcription complex, Characterizing SIVSM proviruses defective in one or both gene s, we found that Vpx is both necessary and sufficient for the nuclear import of the viral reverse transcription complex. In contrast, Vpr, b ut 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 nucle ar transport and cell cycle arrest functions in primate lentivirus bio logy.