Immune responses and viral persistence in SHIV.C.CH848-infected rhesus macaques

Chimeric simian/human immunodeficiency viruses (SHIVs) are widely used in nonhuman primate models to recapitulate HIV infection in humans, yet most SHIVs fail to establish persistent viral infection. We investigated immunological and virological events in rhesus macaques infected with the newly developed SHIV.C.CH848, combined with antiretroviral therapy (cART). Similar to HIV/SIV infection, SHIV.C.CH848 infection established viral reservoirs in CD4+ T cells and myeloid cells, accompanied by productive infection and depletion of CD4+ T cells in systemic and lymphoid tissues throughout SHIV infection. Despite 6-months of cART suppressed viral replication, integrated proviral DNA levels remained stable, especially in CD4+ T cells, and the viral rebound was also observed after ART interruption. Autologous neutralizing antibodies to the parental HIV-1 strain CH848 were detected, with limited viral evolution at 5 months post infection. In comparison, heterogenous neutralizing antibodies in SHIV.C.CH848-infected macaques were not detected except for one (1 of 10) animal at 2 years post infection. These findings suggest that the SHIV.C.CH848, a novel class of transmitted/founder SHIVs, can establish sustained viremia and viral reservoirs in rhesus macaques with clinical immunodeficiency consequences, providing a valuable SHIV model for HIV research.Importance SHIVs have been extensively used in a nonhuman primate (NHP) model for HIV research. Here, we investigate viral reservoir in tissues and immune responses in an NHP model inoculated with newly generated transmitted/founder HIV-1 clade C-based SHIV.C.CH848. The data show T/F SHIVC infection of macaques more closely recapitulates the virologic and clinical features of HIV infection including persistent viremia, and viral rebound once antiretroviral therapy is discontinued. These results suggest this CCR5-tropic, SHIVC virus is valuable for testing responses to HIV vaccines and therapeutics.