Viral burden and disease progression in rhesus monkeys infected with chimeric simian-human immunodeficiency viruses

To determine the role of viral burden in simian-human immunodeficiency viru s (SHIV)-induced disease, cellular provirus and plasma viral RNA levels wer e measured after inoculation of rhesus monkeys with four different SHIVs. T hese SHIVs included SHIV-HXBc2 and SHIV-89.6, constructed with env, tat, re v, and vpu derived from either cell line-passaged or primary patient isolat es of human immunodeficiency virus type 1;the viral quasispecies SHIV-89.6P derived after in vivo passage of SHIV-89.6; and a molecular clone, SHIV-KB 9, derived from SHIV-89.6P. SHIV-HXBc2 and SHIV-89.6 are nonpathogenic in r hesus monkeys; SHIV-89.6P and SHIV-KBS cause rapid CD4(+) T cell depletion and an immunodeficiency syndrome. Relative SHIV provirus levels were highes t during primary infection in monkeys infected with SHIV-89.6P, the virus t hat caused the most rapid and dramatic CD4(+) T cell depletion. However, by 10 weeks postinoculation, provirus levels were similar in monkeys infected with the pathogenic and nonpathogenic chimeric viruses. The virus infectio ns that resulted in the highest peak and chronic viral RNA levels were the pathogenic viruses SHIV-89.6P and SHIV-KBS. SHIV-89.6P uniformly caused rap id and profound CD4(+) T cell depletion and immunodeficiency. Infection wit h the SHIV-KBS resulted in very low CD4(+) T cell counts without seroconver sion in some monkeys and a substantial but less profound CD4(+) T cell depl etion and rapid seroconversion in others. Surprisingly, the level of plasma viremia did not differ between SHIV-KB9-infected animals exhibiting these contrasting outcomes, suggesting that host factors may play an important ro le in AIDS virus pathogenesis. (C) 1999 Academic Press.