Background:  African nonhuman primates (NHP) are thought to be adapted to SIV and, therefore, not to develop AIDS. Three models of SIV infection in natural hosts have been studied to date: African green monkey (AGM), sooty mangabey (SM), and mandrill. These species, despite a high prevalence of SIV infection, resist disease progression for long periods of time. In the wild, due to either a shorter life span or an insufficient follow up of the animals, no AIDS cases were described. However, in captivity, at least one case of immunodeficiency was described in long-term naturally infected animals in each model. Experimental infection of other African NHP—the black mangabeys (BkM), the chimpanzees, and the baboons with heterologous SIV_sm, HIV-1, and HIV-2, have also shown pathogenic potential. Our group documented immunodeficiency in AGM, SM, mandrills, and BkM.

Methods:  Pathological findings of AIDS in SIV-infected African NHP and SIV_mac-infected macaques with terminal disease were characterized by conventional histological methods, e.g., immunohistochemistry and in situ hybridization.

Results:  The naturally SIV_sm-infected SM had an SIV-related immunoblastic B-cell lymphoma. Multinucleated giant cells were present in multiple tissues. The SIV_agm-infected AGM had giant cell disease severely affecting the intestine. Multiple liver and kidney granulomas suggest atypical mycobacteriosis. The animal was co-infected with simian T-cell lymphotropic virus (STLV). The accidentally SIV_sm-infected BkM presented with cachexia due to SIV giant cell colitis and disseminated giant cell disease, with syncytial cells in numerous tissues. The case presented with follicular depletion and lymph node (LN) fibrosis. We determined the phenotype and the SIV-infected cell repartition in tissues.

Conclusion:  Our study showed that neoplasia, severe weight lost, lymphocytic interstitial pneumonia, lymphoid depletion, opportunistic infections, and giant cell disease are present in immunodeficient African NHP. Despite the rarity of immunodeficiency cases in African NHP (which may explain why AIDS went undetected until now), when cases are pulled together the spectrum and the morphology of the lesions are identical to those encountered in macaques with AIDS. Therefore, these “nonpathogenic” models of SIV infection should be reconsidered as “long-term non-progressor” SIV hosts. Since African NHP do, in fact, progress to AIDS, the study of the correlates of immune protection in these models should be useful to depict means for controlling HIV disease.

Keywords: Non Human Primates; AIDS; natural hosts