FATE OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 PROVIRUS IN INFECTED-CELLS - A ROLE FOR VPR

We investigated the fate of human immunodeficiency virus type 1 (HIV-1 ) viral DNA in infected peripheral blood lymphocytes and immortalized T-cell lines by using a replication-defective HIV-1. We observed that integrated HIV-1 DNA and viral gene expression decrease over time. A f rameshift mutation in vpr resulted in maintenance of the HIV-1 proviru s and stable persistence of viral expression. Transfection of vpr toge ther,vith the neomycin resistance gene in the absence of other viral g enes decreased the formation of geneticin-resistant colonies, indicati ng either a cytotoxic or a cytostatic effect upon cells. Therefore, ma intenance of HIV-1 infection within an infected proliferating populati on is due to two competing processes, the rate of viral spread and the degree of cell growth inhibition and/or death induced by Vpr.