HIV-2 Surveillance with Next-Generation Sequencing Reveals Mutations in a Cytotoxic Lymphocyte-Restricted Epitope Involved in Long-Term Nonprogression

Abstract

HIV-2 exhibits a natural history of infection distinct from HIV-1. Primarily found in West Africa and in only 10%–20% of HIV infections in this region, patients with HIV-2 typically exhibit a slower progression to AIDS, lower viral loads, and decreased rates of transmission. Here, we used next-generation sequencing to determine the sequence and phylogenetic classification of nine HIV-2 genomes. We identified a patient with a series of mutations in an invariant cytotoxic lymphocyte (CTL)-restricted gag epitope required for retroviral structure and replication and implicated in long-term nonprogression to AIDS. The presence of wild-type sequence argues these mutations are involved in immune escape, whereas its reversion to a sequence seen only in the sooty mangabey reservoir suggests an alternate means of controlling infection. Surveillance and molecular characterization of circulating strains are essential for continued development of monitoring tools and may provide greater insight into the reduced pathogenicity of HIV-2.