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 Siliciano; Greg M Laird; Dan H Barouch; Janice E Clements; Robert F Siliciano

doi:10.1016/j.chom.2019.06.005

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.

Authors

Alexandra M Bender¹, Francesco R Simonetti¹, Mithra R Kumar¹, Emily J Fray¹, Katherine M Bruner¹, Andrew E Timmons¹, Katherine Y Tai¹, Katharine M Jenike¹, Annukka A R Antar¹, Po-Ting Liu², Ya-Chi Ho¹, Dana N Raugi³, Moussa Seydi⁴, Geoffrey S Gottlieb³, Afam A Okoye⁵, Gregory Q Del Prete⁶, Louis J Picker⁵, Joseph L Mankowski⁷, Jeffrey D Lifson⁶, Janet D Siliciano¹, Greg M Laird⁸, Dan H Barouch², Janice E Clements⁷, Robert F Siliciano⁹

Affiliations

¹ Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
² Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
³ Department of Medicine & Center of Emerging & Re-Emerging Infectious Diseases, University of Washington, Seattle, WA, USA.
⁴ Service de Maladies Infectieuses et Tropicales, CHNU-Fann, Dakar, Senegal.
⁵ Vaccine and Gene Therapy Institute, Oregon Health and Sciences University, Beaverton, OR, USA.
⁶ AIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, MD, USA.
⁷ Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁸ Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Accelevir Diagnostics, Baltimore, MD, USA.
⁹ Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Howard Hughes Medical Institute, Baltimore, MD 21205, USA. Electronic address: [email protected].

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.

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

Substances

Anti-Retroviral Agents

Abstract

Publication types

MeSH terms

Substances

Grants and funding