PROGRESSION TO AIDS IN THE ABSENCE OF A GENE FOR VPR OR VPX

Rhesus monkeys (Macaca mulatta) were experimentally infected with stra ins of simian immunodeficiency virus (SIV) derived from SIV(mac)239 la cking vpr, vpx, or both vpr and vpx genes, These auxiliary genes are n ot required for virus replication in cultured cells but are consistent ly conserved within the SIVmac/human immunodeficiency virus type 2/SIV sm group of primate lentiviruses. All four rhesus monkeys infected wit h the vpr deletion mutant showed an early spike in plasma antigenemia, maintained high virus burdens, exhibited declines in CD4(+) lymphocyt e concentrations, and had significant changes in lymph node morphology , and two have died to date with AIDS, The behavior of the vpr deletio n mutant was indistinguishable from that of the parental, wild-type vi rus, Rhesus monkeys infected with the vpx deletion mutant showed lower levels of plasma antigenemia, lower virus burdens, and delayed declin es in CD4(+) lymphocyte concentrations but nonetheless progressed with AIDS to a terminal stage, The vpr + vpx double mutant was severely at tenuated, with much lower virus burdens and no evidence of disease pro gression, These and other results indicate that vpr provides only a sl ight facilitating advantage for wild-type SIVmac replication in vivo. Thus, progression to AIDS and death can occur in the absence of a gene for vpr or vpx.