Changes in simian immunodeficiency virus reverse transcriptase alleles that appear during infection of macaques enhance infectivity and replication in CD4+ T cells

We previously showed that a slowly replicating, minimally pathogenic clone of simian immunodeficiency virus (SIV), SIVmneCl8, evolves increased ability to replicate in T cells with the onset of AIDS in pig-tailed macaques. Moreover, molecular clones derived from late stages of infection (SIVmne170 and SIVmne027) replicate to high levels in vivo compared to SIVmneCl8. Here, we investigated the role of rt mutations in SIVmne variant replication. We demonstrate selection for rt alleles that enhance viral infectivity and replication capacity in CD4+ T cells. Moreover, the ability of SIVmne to be induced from resting CD4+ T cells by anti-CD3/CD28 stimulation is more strongly influenced by the variant rt alleles than nef alleles. Taken together, our data underscore the importance of RT determinants for pathogenicity of SIV and for the capacity to replicate in CD4+ T cell populations.