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<p>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 <i>IL1B</i> 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 <i>IL1B</i> expression associates inversely with reservoir size at higher frequencies of central memory CD4+ T cells, linking monocyte <i>IL1B</i> 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 <i>IL1B</i> expression could decrease HIV-1 proviral reservoirs in individuals initiating ART during acute infection.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月29日

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  • 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

摘要

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.