Macaque species susceptibility to simian immunodef

Authors: Sarah E Beck Kathleen M Kelly Suzanne E Queen Robert J Adams M Christine Zink Patrick M Tarwater Joseph L Mankowski

Publish Date: 2015/02/12

Volume: 21, Issue: 2, Pages: 148-158

PDF Link

Abstract

Immune pressure exerted by MHC class Irestricted 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 cellmediated 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/17EFr pigtailed macaques progressed more rapidly to AIDS had higher plasma and cerebrospinal fluid CSF viral loads and were more likely to progress to SIVassociated encephalitis SIVE compared to rhesus macaques In addition MHC class I alleles were neuroprotective in both species MamuA001 in rhesus macaques and ManeA10840101 in pigtailed macaques animals expressing these alleles were less likely to develop SIV encephalitis and correspondingly had lower viral replication in the brain Speciesspecific differences in susceptibility to SIV disease demonstrated that cell mediated immune responses are critical to SIV CNS disease progression

Keywords: