Efficient Mucosal Transmissibility but Limited Pathogenicity of R5 SHIVSF162P3N in Chinese-Origin Rhesus Macaques

Abstract

Infection of rhesus macaques (RMs) of Indian origin with simian immunodeficiency virus or simian-HIV (SHIV) provided powerful tools to study HIV-1 transmission and disease and for testing the efficacy of novel drugs, vaccines, and prevention strategies. In developing alternative nonhuman primate AIDS models for the CCR5 (R5)-tropic SHIVSF162P3N, we characterized virus transmission and infection in Chinese-origin RMs. Virologic, immunologic, and pathogenic evaluations of R5 SHIVSF162P3N infection in Chinese RMs challenged intrarectally (ir) or intravaginally were performed and compared with those previously observed in Indian-origin rhesus exposed to the same inoculum dose and via similar route. R5 SHIVSF162P3N transmits efficiently across mucosal surfaces in Chinese RMs. The magnitude and kinetics of early virus dissemination after ir inoculation in the Chinese macaques were similar to those observed in Indian rhesus, but a trend toward increased SHIVSF162P3N vaginal infectivity and rapid virus spread was seen in the Chinese macaques compared with the Indian-origin animals. Once infected, however, set point viremia in the ir- and intravaginal-infected Chinese rhesus was significantly lower and the animals survived longer compared with infected Indian rhesus. The R5 SHIVSF162P3N/Chinese RM infection model is suitable for studies of mucosal HIV-1 transmission and protection, but the high frequency of spontaneous control of chronic viremia and reduced virulence with SHIVSF162P3N in this macaque subspecies may limit its utility in studying HIV-1 pathogenesis and in evaluating vaccines and antiretrovirals that rely on reduction in chronic viral load or AIDS development as an experimental end point.