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

Alexandra M. Bender, Francesco R. Simonetti, Mithra R. Kumar, Emily J. Fray, Katherine M. Bruner, Andrew E. Timmons, Katherine Y. Tai, Katharine M. Jenike, Annukka A.R. Antar, Po Ting Liu, Ya Chi Ho, Dana N. Raugi, Moussa Seydi, Geoffrey S. Gottlieb, Afam A. Okoye, Gregory Q. Del Prete, Louis J. Picker, Joseph L. Mankowski, Jeffrey D. Lifson, Janet D. SilicianoGreg M. Laird, D. H. Barouch, Janice E. Clements, Robert F. Siliciano

Research output: Contribution to journalArticle

Abstract

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. Understanding the proviral landscape in ART-treated non-human primates (NHP) is crucial before using them to test HIV cure strategies. Bender et al. report that while most proviruses persisting in ART-treated SIV-infected NHPs are defective, there is a significantly higher fraction of intact genomes compared to ART-treated HIV-1-infected humans.

Original languageEnglish (US)
Pages (from-to)73-85.e4
JournalCell Host and Microbe
Volume26
Issue number1
DOIs
StatePublished - Jul 10 2019

Keywords

  • HIV-2
  • SHIV
  • SIV
  • clonal expansion
  • defective provirus
  • latent reservoir

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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    Bender, A. M., Simonetti, F. R., Kumar, M. R., Fray, E. J., Bruner, K. M., Timmons, A. E., Tai, K. Y., Jenike, K. M., Antar, A. A. R., Liu, P. T., Ho, Y. C., Raugi, D. N., Seydi, M., Gottlieb, G. S., Okoye, A. A., Del Prete, G. Q., Picker, L. J., Mankowski, J. L., Lifson, J. D., ... Siliciano, R. F. (2019). The Landscape of Persistent Viral Genomes in ART-Treated SIV, SHIV, and HIV-2 Infections. Cell Host and Microbe, 26(1), 73-85.e4. https://doi.org/10.1016/j.chom.2019.06.005