DIVERSE HOST RESPONSES AND OUTCOMES FOLLOWING SIMIAN IMMUNODEFICIENCYVIRUS SIVMAC239 INFECTION IN SOOTY MANGABEYS AND RHESUS MACAQUES

Sooty mangabeys naturally infected with simian immunodeficiency virus (SIV) do not develop immunodeficiency despite the presence of viral lo ads of 10(5) to 10(7) RNA copies/ml. To investigate the basis of apath ogenic SIV infection in sooty mangabeys, three sooty mangabeys and thr ee rhesus macaques were inoculated intravenously with SIVmac239 and ev aluated longitudinally for 1 year. SIVmac239 infection of sooty mangab eys resulted in 2- to 4-log-lower viral loads than in macaques and did not reproduce the high viral loads observed in natural SIVsmm infecti on. During acute SIV infection, polyclonal cytotoxic T-lymphocyte (CTL ) activity coincident with decline in peak plasma viremia was observed in both macaques and mangabeys; 8 to 20 weeks later, CTL activity dec lined in the macaques but was sustained and broadly directed in the ma ngabeys. Neutralizing antibodies to SIVmac239 were detected in the mac aques but not the mangabeys. Differences in expression of CD38 on CD8( +) T lymphocytes or in the percentage of naive phenotype T cells expre ssing CD45RA and CD62L-selection did not correlate with development of AIDS in rhesus macaques. In macaques, the proportion of CD4(+) T lymp hocytes expressing CD25 declined during SIV infection, while in mangab eys, CD25-expressing CD4+ T lymphocytes increased. Longitudinal evalua tion of cytokine secretion by flow cytometric analysis of unstimulated lymphocytes revealed elevation of interleukin-2 and gamma interferon in a macaque and only interleukin-10 in a concurrently infected mangab ey during acute SIV infection. Differences in host responses following experimental SIVmac239 infection may be associated with the divergent outcome in sooty mangabeys and rhesus macaques.