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

Author

Listed:
  • Philip K. Ehrenberg

    (Walter Reed Army Institute of Research)

  • Aviva Geretz

    (Walter Reed Army Institute of Research
    Henry M. Jackson Foundation for the Advancement of Military Medicine)

  • Meta Volcic

    (Ulm University Medical Center)

  • Taisuke Izumi

    (Walter Reed Army Institute of Research
    Henry M. Jackson Foundation for the Advancement of Military Medicine
    American University
    District of Columbia Center for AIDS Research)

  • Lauren K. Yum

    (Walter Reed Army Institute of Research
    Henry M. Jackson Foundation for the Advancement of Military Medicine)

  • Adam Waickman

    (Walter Reed Army Institute of Research
    State University of New York Upstate Medical University)

  • Shida Shangguan

    (Walter Reed Army Institute of Research
    Henry M. Jackson Foundation for the Advancement of Military Medicine)

  • Dominic Paquin-Proulx

    (Walter Reed Army Institute of Research
    Henry M. Jackson Foundation for the Advancement of Military Medicine)

  • Matthew Creegan

    (Walter Reed Army Institute of Research
    Henry M. Jackson Foundation for the Advancement of Military Medicine)

  • Meera Bose

    (Walter Reed Army Institute of Research
    Henry M. Jackson Foundation for the Advancement of Military Medicine)

  • Kawthar Machmach

    (Walter Reed Army Institute of Research
    Henry M. Jackson Foundation for the Advancement of Military Medicine)

  • Aidan McGraw

    (American University)

  • Akshara Narahari

    (Saint Joseph’s University)

  • Jeffrey R. Currier

    (Walter Reed Army Institute of Research)

  • Carlo Sacdalan

    (SEARCH Research Foundation
    Chulalongkorn University)

  • Nittaya Phanuphak

    (Institute of HIV Research and Innovation)

  • Richard Apps

    (National Institutes of Health)

  • Michael Corley

    (Weill Cornell Medicine
    University of California)

  • Lishomwa C. Ndhlovu

    (Weill Cornell Medicine)

  • Bonnie Slike

    (Walter Reed Army Institute of Research
    Henry M. Jackson Foundation for the Advancement of Military Medicine)

  • Shelly J. Krebs

    (Walter Reed Army Institute of Research)

  • Jintanat Anonworanich

    (Walter Reed Army Institute of Research
    Henry M. Jackson Foundation for the Advancement of Military Medicine)

  • Sodsai Tovanabutra

    (Walter Reed Army Institute of Research
    Henry M. Jackson Foundation for the Advancement of Military Medicine)

  • Merlin L. Robb

    (Walter Reed Army Institute of Research
    Henry M. Jackson Foundation for the Advancement of Military Medicine)

  • Michael A. Eller

    (Walter Reed Army Institute of Research
    Henry M. Jackson Foundation for the Advancement of Military Medicine
    National Institutes of Health (NIH))

  • Gregory M. Laird

    (Accelevir Diagnostics)

  • Joshua Cyktor

    (University of Pittsburgh)

  • Eric S. Daar

    (Lundquist Institute at Harbor-UCLA Medical Center)

  • Trevor A. Crowell

    (Walter Reed Army Institute of Research
    Henry M. Jackson Foundation for the Advancement of Military Medicine)

  • John W. Mellors

    (University of Pittsburgh)

  • Sandhya Vasan

    (Walter Reed Army Institute of Research
    Henry M. Jackson Foundation for the Advancement of Military Medicine)

  • Nelson L. Michael

    (Walter Reed Army Institute of Research)

  • Frank Kirchhoff

    (Ulm University Medical Center)

  • Rasmi Thomas

    (Walter Reed Army Institute of Research)

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.

Suggested Citation

  • 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 McG, 2025. "Single-cell analyses identify monocyte gene expression profiles that influence HIV-1 reservoir size in acutely treated cohorts," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59833-9
    DOI: 10.1038/s41467-025-59833-9
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