Macaque species susceptibility to simian immunodeficiency virus: increased incidence of SIV central nervous system disease in pigtailed macaques versus rhesus macaques

Immune pressure exerted by MHC class I-restricted cytotoxic T cells drives the development of viral escape mutations, thereby regulating HIV disease progression. Nonetheless, the relationship between host immunity and HIV central nervous system (CNS) disease remains poorly understood. The simian immunodeficiency virus (SIV) macaque model recapitulates key features of HIV infection including development of AIDS and CNS disease. To investigate cell-mediated immunity regulating SIV CNS disease progression, we compared the incidence of SIV encephalitis and the influence of MHC class I allele expression on the development of CNS disease in rhesus macaques (Macaca mulatta) versus pigtailed macaques (Macaca nemestrina). After inoculation with the immunosuppressive swarm SIV/DeltaB670 and the neurovirulent molecular clone SIV/17E-Fr, pigtailed macaques progressed more rapidly to AIDS, had higher plasma and cerebrospinal fluid (CSF) viral loads, and were more likely to progress to SIV-associated encephalitis (SIVE) compared to rhesus macaques. In addition, MHC class I alleles were neuroprotective in both species (Mamu-A*001 in rhesus macaques and Mane-A1*084:01:01 in pigtailed macaques); animals expressing these alleles were less likely to develop SIV encephalitis and correspondingly had lower viral replication in the brain. Species-specific differences in susceptibility to SIV disease demonstrated that cell mediated immune responses are critical to SIV CNS disease progression.