The HIV-2 proviral landscape is dominated by defective proviruses

AIDS. 2024 Mar 1;38(3):309-316. doi: 10.1097/QAD.0000000000003776. Epub 2023 Nov 22.

Abstract

Background: Compared with HIV-1 infection, HIV-2 infection is associated with a slower progression to AIDS. Understanding the persistence of HIV-2 infection might inform the mechanisms responsible for differences in the pathogenicity of HIV-2 versus HIV-1.

Methods: In this study, we analyzed the genetic composition of the proviral reservoir in archived blood samples collected from 13 untreated HIV-2-infected adults from Senegal. We used single-genome, near-full-length individual proviral sequencing (FLIP-Seq) to assess the relative frequency of intact and defective proviruses.

Results: Ten out of 13 (77%) study participants demonstrated virologic suppression (<90 HIV RNA copies/ml) while the remaining 3 (23%) had detectable HIV RNA. We obtained 363 proviral sequences from peripheral blood mononuclear cells (PBMCs) from the 13 study participants. Within these sequences, 342 (94%) defective proviruses were detected. Twenty-one (6%) intact proviruses were detected from three study participants, with one study participant displaying a large clone consisting of 16 genome-intact sequences.

Conclusion: This data suggests that similar to HIV-1 infection, the proviral landscape of HIV-2 is dominated by defective proviruses.

MeSH terms

  • Adult
  • CD4-Positive T-Lymphocytes
  • HIV Infections*
  • HIV-2 / genetics
  • Humans
  • Leukocytes, Mononuclear
  • Proviruses* / genetics
  • RNA
  • Viral Load

Substances

  • RNA