Single-cell analyses identify monocyte gene expression profiles that influence HIV-1 reservoir size in acutely treated cohorts

Eliminating latent HIV-1 is a major goal of AIDS research but host factors determining the size of these reservoirs are poorly understood. Here, we investigate the role of host gene expression on HIV-1 reservoir size during suppressive antiretroviral therapy (ART). Peripheral blood cells of fourteen males initiating ART during acute infection and demonstrating effective viral suppression but varying magnitudes of total HIV-1 DNA were characterized by single-cell RNA sequencing. Differential expression analysis demonstrates increased CD14+ monocyte activity in participants having undetectable HIV-1 reservoirs, with IL1B expression inversely associating with reservoir size. This is validated in another cohort of 38 males comprised of different ancestry and HIV-1 subtypes, and with intact proviral DNA assay (IPDA®) measurements. Modeling interactions show monocyte IL1B expression associates inversely with reservoir size at higher frequencies of central memory CD4+ T cells, linking monocyte IL1B expression to cell types known to be reservoirs for persistent HIV-1. Functional analyses reveal that IL1B activates NF-κB, thereby promoting productive HIV-1 infection while simultaneously suppressing viral spread, suggesting a natural latency reversing activity to deplete the reservoir in ART-treated individuals. Altogether, scRNA-seq analyses reveal that monocyte IL1B expression could decrease HIV-1 proviral reservoirs in individuals initiating ART during acute infection.

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Publication Details

Journal
Nature Communications
Published
2025-05-29
DOI
https://doi.org/10.1038/s41467-025-59833-9
Citations
5
Primary Topic
HIV Research and Treatment
Type
article
Field-Weighted Citation Impact
5.18

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article

Single-cell analyses identify monocyte gene expression profiles that influence HIV-1 reservoir size in acutely treated cohorts

Lishomwa C. Ndhlovu, Sodsai Tovanabutra, Shida Shangguan, Jeffrey R. Currier et al.
5 citations
Nature Communications
HIV Research and Treatment
5.18
article

Single-cell analyses identify monocyte gene expression profiles that influence HIV-1 reservoir size in acutely treated cohorts

Lishomwa C. Ndhlovu, Sodsai Tovanabutra, Shida Shangguan, Jeffrey R. Currier, Meta Volčič, Dominic Paquin‐Proulx, Michael A. Eller, Nelson L. Michael, John W. Mellors, Sandhya Vasan, Kawthar Machmach, Aviva Geretz, T Izumi, Nittaya Phanuphak, Carlo Sacdalan, Joshua C. Cyktor, Jintanat Ananworanich, Bonnie M. Slike, Shelly J. Krebs, Philip K. Ehrenberg, Rasmi Thomas, Trevor A. Crowell, Meera Bose, Frank Kirchhoff, Gregory M. Laird, Merlin L. Robb, Eric S. Daar, Adam T. Waickman, Lauren K. Yum, Matthew Creegan, Michael J. Corley, Richard Apps, Aidan McGraw, Akshara Narahari
article en
5 citations

Abstract

Eliminating latent HIV-1 is a major goal of AIDS research but host factors determining the size of these reservoirs are poorly understood. Here, we investigate the role of host gene expression on HIV-1 reservoir size during suppressive antiretroviral therapy (ART). Peripheral blood cells of fourteen males initiating ART during acute infection and demonstrating effective viral suppression but varying magnitudes of total HIV-1 DNA were characterized by single-cell RNA sequencing. Differential expression analysis demonstrates increased CD14+ monocyte activity in participants having undetectable HIV-1 reservoirs, with IL1B expression inversely associating with reservoir size. This is validated in another cohort of 38 males comprised of different ancestry and HIV-1 subtypes, and with intact proviral DNA assay (IPDA®) measurements. Modeling interactions show monocyte IL1B expression associates inversely with reservoir size at higher frequencies of central memory CD4+ T cells, linking monocyte IL1B expression to cell types known to be reservoirs for persistent HIV-1. Functional analyses reveal that IL1B activates NF-κB, thereby promoting productive HIV-1 infection while simultaneously suppressing viral spread, suggesting a natural latency reversing activity to deplete the reservoir in ART-treated individuals. Altogether, scRNA-seq analyses reveal that monocyte IL1B expression could decrease HIV-1 proviral reservoirs in individuals initiating ART during acute infection.

Nature CommunicationsVol. 16(1)
Henry M. Jackson Foundation (US), National Institutes of Health (US), Chulalongkorn University (TH), University of Pittsburgh (US), American University (US), Universität Ulm (DE), SUNY Upstate Medical University (US), Cornell University (US), UCLA Medical Center (US), AIDS United (US), National Human Genome Research Institute (US), HIV Netherlands Australia Thailand Research Collaboration (TH), National Institute of Allergy and Infectious Diseases (US), Institute on Aging (US), Office of AIDS Research (US), Harbor–UCLA Medical Center (US), Weill Cornell Medicine (US), Johns Hopkins University Center for AIDS Research, Saint Joseph's University (US), Walter Reed Army Institute of Research (US)
U.S. Department of Defense, U.S. Department of Health and Human Services, Henry M. Jackson Foundation, Gilead Sciences, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, ViiV Healthcare, ACT Government, Deutsche Forschungsgemeinschaft, National Institutes of Health, Centers for Disease Control and Prevention, U.S. Public Health Service, National Institute of Allergy and Infectious Diseases, U.S. Military HIV Research Program, NHLBI Division of Intramural Research
Good health and well-being
Openalex Percentile: Top 5%
HIV Research and Treatment
5.18
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