The Landscape of Persistent Viral Genomes in ART-Treated SIV, SHIV, and HIV-2 Infections

Cell Host Microbe. 2019 Jul 10;26(1):73-85.e4. doi: 10.1016/j.chom.2019.06.005.


Evaluation of HIV cure strategies is complicated by defective proviruses that persist in ART-treated patients but are irrelevant to cure. Non-human primates (NHP) are essential for testing cure strategies. However, the persisting proviral landscape in ART-treated NHPs is uncharacterized. Here, we describe viral genomes persisting in ART-treated, simian immunodeficiency virus (SIV)-infected NHPs, simian-human immunodeficiency virus (SHIV)-infected NHPs, and humans infected with HIV-2, an SIV-related virus. The landscapes of persisting SIV, SHIV, and HIV-2 genomes are also dominated by defective sequences. However, there was a significantly higher fraction of intact SIV proviral genomes compared to ART-treated HIV-1 or HIV-2 infected humans. Compared to humans with HIV-1, SIV-infected NHPs had more hypermutated genomes, a relative paucity of clonal SIV sequences, and a lower frequency of deleted genomes. Finally, we report an assay for measuring intact SIV genomes which may have value in cure research.

Keywords: HIV-2; SHIV; SIV; clonal expansion; defective provirus; latent reservoir.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Retroviral Agents / therapeutic use*
  • Defective Viruses / genetics
  • Genetic Variation*
  • Genome, Viral
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV-1 / classification
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • HIV-2 / classification
  • HIV-2 / drug effects*
  • HIV-2 / genetics
  • Humans
  • Macaca mulatta
  • Proviruses / genetics
  • Simian Acquired Immunodeficiency Syndrome / drug therapy*
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus / classification
  • Simian Immunodeficiency Virus / drug effects*
  • Simian Immunodeficiency Virus / genetics


  • Anti-Retroviral Agents