Differential apoptosis effects of primate lentiviral Vpr and Vpx in mammalian cells

The growth inhibitory effects of Vpr and Vpx are species and cell type-depe ndent, HIV-1, HIV-2 and SIV Vpr are primarily cytostatic in mammalian cells and HIV-1 Vpr has been reported to induce apoptosis in human cells. Our pr evious studies have shown that HIV-1, HIV-2 and SIV Vpr and Vpx have differ ential cytostatic and cytotoxic effects in the yeast cells [Zhang et al.: V irology, 230:103-112; '1997], Here, we further examined the apoptosis funct ion of HIV-1 Vpr in different species of mammalian cells and investigated i f other primate lentiviral Vpr and Vpx exert similar functions. Our results show that none of the primate lentiviral Vpr or Vpx we tested induces apop tosis in nonhuman species of mammalian cells. However, HIV-1 Vpr, but not H IV-2 or SIV Vpr and/or Vpx, induced apoptosis in different types of human c ell lines. Further, the apoptotic effect of HIV-1 Vpr can be distinguished from that of the human interferon-gamma, a known proapoptotic protein, that HIV-1 Vpr shows little to no paracrine and/or bystander effect. When coexp ressed with Bcl-2 or Bcl-X-L, the apoptotic effect of HIV-1 Vpr became mark edly attenuated. These results indicate that the apoptotic effect of HIV-1 Vpr is species-dependent and is intracellularly modulated by the Bcl-2 fami ly of proteins. Our study also suggests that the proapoptotic function of H IV-1 Vpr is developmentally associated with human but not nonhuman primate species, Copyright (C) 2000 National Science Council, ROC and S. Karger AG, Basel.