We previously reported that a macaque-tropic HIV-1 efficiently replicates in peripheral blood mononuclear cells of cynomolgus macaques; However, the macaques infected with the HIV-1 displayed low viral loads during the acute phase with subsequent short-term viremia. These virological phenotypes in vivo differed from those observed in most HIV-1-infected humans.

​

In this study, we found that serial in vivo passages of a CCR5-tropic HIV-1mt, AS38 resulted in higher viral loads during the acute phase and prolonged periods of persistent viremia. Whole-genome sequencing in the in vivo-growing HIV-1 demonstrated that the emergence of a unique 15-nt deletion within the vif gene, which resulted in a significant increase in Vpr protein expression without affecting Vif-mediated function to antagonize antiretroviral host factors APOBEC3s. These results indicate that Vpr may play a critical role for HIV-1 replication in the macaques.