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Tracking HIV persistence across T cell lineages during early ART-treated HIV-1-infection using a reservoir-marking humanized mouse model

Author

Listed:
  • Namita Satija

    (Icahn School of Medicine at Mount Sinai)

  • Foramben Patel

    (Icahn School of Medicine at Mount Sinai)

  • Gerrit Schmidt

    (Icahn School of Medicine at Mount Sinai)

  • Donald V. Doanman

    (Icahn School of Medicine at Mount Sinai)

  • Manav Kapoor

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Annalena Porte

    (Icahn School of Medicine at Mount Sinai)

  • Ying-Chih Wang

    (Icahn School of Medicine at Mount Sinai)

  • Kenneth M. Law

    (Icahn School of Medicine at Mount Sinai
    Lexeo Therapeutics)

  • Anthony M. Esposito

    (New Jersey City University)

  • Kimaada Allette

    (Icahn School of Medicine at Mount Sinai)

  • Kristin G. Beaumont

    (Icahn School of Medicine at Mount Sinai)

  • Robert P. Sebra

    (Icahn School of Medicine at Mount Sinai)

  • Benjamin K. Chen

    (Icahn School of Medicine at Mount Sinai)

Abstract

Human immunodeficiency virus (HIV) infection depletes CD4 T-cells, and long-term persistence of latent virus prevents full clearance of HIV even in the presence of effective antiretroviral therapy (ART), Here we present the HIV-1-induced lineage tracing (HILT) system, a model that irreversibly marks infected cells within a humanized mouse model, which detects rare latently infected cells. Immunodeficient mice transplanted with genetically modified hematopoietic stem cells develop a human immune system, in which CD4 T-cells contain a genetic switch that permanently labels cells infected by HIV-1 expressing cre-recombinase. Through single-cell RNA sequencing of HILT-marked cells during acute infection and post-ART treatment, we identify distinct CD4+ T-cell transcriptional lineages enriched in either active or latent infections. Comparative gene expression analysis highlights common pathways modulated in both states, including EIF2, Sirtuin, and protein ubiquitination. Critical regulators of these pathways, including JUN, BCL2, and MDM2, change to opposite directions in the two states, highlighting gene expression programs that may support HIV persistence across T-cell lineages and states.

Suggested Citation

  • Namita Satija & Foramben Patel & Gerrit Schmidt & Donald V. Doanman & Manav Kapoor & Annalena Porte & Ying-Chih Wang & Kenneth M. Law & Anthony M. Esposito & Kimaada Allette & Kristin G. Beaumont & Ro, 2025. "Tracking HIV persistence across T cell lineages during early ART-treated HIV-1-infection using a reservoir-marking humanized mouse model," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57368-7
    DOI: 10.1038/s41467-025-57368-7
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    References listed on IDEAS

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