HIGH VIRAL LOAD AND CD4 LYMPHOPENIA IN RHESUS AND CYNOMOLGUS MACAQUESINFECTED BY A CHIMERIC PRIMATE LENTIVIRUS CONSTRUCTED USING THE ENV, REV, TAT, AND VPU GENES FROM HIV-1 LAI

Chimeric primate lentiviruses composed of SIV and HIV genes may allow the analysis of the role of these discrete HIV genes in viral pathogen esis in macaque monkeys. We have constructed a chimeric virus in which the env, rev, tat, and vpu genes of HIV-1 Lai replace the env, rev, a nd tar genes of the SIVmac239 genome. This virus, SHIVsbg, replicates efficiently in rhesus (Indian and Chinese subspecies) and cynomolgus m onkeys with viral loads in PBMC and lymph nodes of up to one infected cell per 30 cells during the acute phase of the infection. Sera from a ll monkeys recognize specific HIV-1 glycoproteins. The onset of lympha denopathy in all animals was concurrent with a depletion of CD4 lympho cytes in peripheral blood. The virulence of this SHIV for rhesus and c ynomolgus monkeys therefore closely parallels that of HIV-1 for human in the acute phase of the infection. Changes in the env and vpu genes of a molecular clone of HIV-1 can now be analyzed after passage in non human primate species as the SHIVsbg replicates efficiently. The SHIVs bg-macaque model is an important step in the development of a readily available animal model for HIV-1 vaccine studies. (C) 1996 Academic Pr ess, Inc.