VPR STIMULATES VIRAL EXPRESSION AND INDUCES CELL-KILLING IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE 1-INFECTED DIVIDING JURKAT T-CELLS

In this study we investigated the effects of Vpr during human immunode ficiency virus (HIV) infection of proliferating Jurkat T cells by usin g a vesicular stomatitis virus envelope G glycoprotein pseudotyped HIV superinfection system, We observe that the expression of Vpr results in a severe reduction in the life span of HIV type 1 (HIV-1)-infected dividing T cells in culture. In agreement with a recent report (S. A. Stewart, B. Poon, J. B. M. Jowett, and I. S. Chen, J. Virol, 71:5579-5 592, 1997), we show that events characteristic of apoptotic cell death are involved in the Vpr-mediated cytopathic effects. Our results also show that infection with viruses expressing the wild-type vpr gene re sults in an increase in viral gene expression and production, Interest ingly, the effects of Vpr on cell viability and on viral gene expressi on both correlate with the ability of the protein to induce a cell cyc le arrest in the G(2)/M phase. Mutagenesis analyses show that the C te rminus of Vpr is essential for these biological activities. Although t he role of Vpr is currently associated with the infection of nondividi ng cells, our results suggest that Vpr can also directly increase vira l replication in vivo in infected dividing T cells. Furthermore, these in vitro observations suggest that Vpr-mediated cytotoxic effects cou ld contribute to the CD4(+) depletion associated with AIDS progression .