SIV(mac) pathogenesis in rhesus macaques of Chinese and Indian origin compared with primary HIV infections in humans

Abstract

Objective: To develop a SIV-rhesus macaque (Rh) model of AIDS that more closely approximates HIV pathogenesis in humans.

Design: The pathogenesis of SIV was compared in two different types of Rh, the Chinese (Ch) and Indian (Ind) subspecies.

Methods: Ch Rh and Ind Rh origin were identified genetically and infected with the SIV(mac)239 molecular clone. Plasma viral loads, depletion of intestinal lymphocytes with memory phenotype, humoral immune responses and CD4/CD8 cell ratios were compared during acute and steady-state periods of infection.

Results: Plasma viral loads from 7 days after infection through 240 days were significantly lower in Rh of Ch origin compared with Ind Rh. Viral loads in Ch Rh were closer to viral loads observed in untreated humans infected with HIV-1. Depletion of intestinal effector cells was less evident in SIV-infected Ch Rh compared with Ind Rh. An index of intestinal pathogenesis was devised that closely paralleled viral load and severity of infection. There were no rapid progressors to AIDS among 10 Ch Rh. In contrast, three of four Ind Rh progressed rapidly to AIDS.

Conclusions: Compared with Ind Rh, SIV(mac) pathogenesis in Ch Rh was closer to HIV-1 infections in untreated adult humans. The differences were statistically significant. The Ch Rh subspecies is a suitable AIDS model and may have advantages over the rapid and highly pathogenic Ind Rh model. Moreover, Ind Rh supplies are limited and use of Ch Rh provides a new resource.