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

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

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...

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Main Authors: Philip K. Ehrenberg, Aviva Geretz, Meta Volcic, Taisuke Izumi, Lauren K. Yum, Adam Waickman, Shida Shangguan, Dominic Paquin-Proulx, Matthew Creegan, Meera Bose, Kawthar Machmach, Aidan McGraw, Akshara Narahari, Jeffrey R. Currier, Carlo Sacdalan, Nittaya Phanuphak, Richard Apps, Michael Corley, Lishomwa C. Ndhlovu, Bonnie Slike, Shelly J. Krebs, Jintanat Anonworanich, Sodsai Tovanabutra, Merlin L. Robb, Michael A. Eller, Gregory M. Laird, Joshua Cyktor, Eric S. Daar, Trevor A. Crowell, John W. Mellors, Sandhya Vasan, Nelson L. Michael, Frank Kirchhoff, Rasmi Thomas
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-59833-9
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Summary: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.
ISSN:2041-1723

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