RHESUS MACAQUES THAT BECOME SYSTEMICALLY INFECTED WITH PATHOGENIC SHIV 89.6-PD AFTER INTRAVENOUS, RECTAL, OR VAGINAL INOCULATION AND FAIL TO MAKE AN ANTIVIRAL ANTIBODY-RESPONSE RAPIDLY DEVELOP AIDS

A new simian-human immunodeficiency virus (SHIV) stock (SHIV 89.6-PD), derived from plasma of a rhesus macaque used for in vivo serial passa ge of virulence-attenuated SHIV 89.6, produces systemic infection afte r intravenous, intravaginal, or intrarectal inoculation of rhesus maca ques. Infection with this virus results in high levels of viral antige n in plasma, a precipitous decline in CD4(+) T-cell counts, and a dise ase syndrome that is characteristic of AIDS. Rapid progression to dise ase was associated with failure to seroconvert to viral antigens, wher eas longer survival was associated with production of antiviral antibo dies. In Intravenously inoculated animals, peak antigenemia occurred a t 7 days postinjection (PI) and severe CD4(+) depletion occurred at 14 days PI. In mucosally infected animals,peak antigenemia occurred at 1 4 days PI and severe CD4(+) depletion was not evident until 21 days PI . The I-week delay in both viral antigenemia and CD4(+) T-cell decline in mucosally infected animals is consistent with the hypothesis that, following vaginal inoculation, virus dissemination proceeds in a step wise manner from the mucosal surface to the draining lymph nodes and s ubsequently to the bloodstream This animal model can be used to test t he ability of HIV-1 envelope-based vaccines to prevent infection or di sease after challenge by the three major routes of HIV transmission.