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Single-cell TCR sequencing reveals phenotypically diverse clonally expanded cells harboring inducible HIV proviruses during ART

Author

Listed:
  • Pierre Gantner

    (Université de Montréal)

  • Amélie Pagliuzza

    (Centre de Recherche du Centre Hospitalier de l’Université de Montréal)

  • Marion Pardons

    (Université de Montréal)

  • Moti Ramgopal

    (Midway Immunology & Research Center)

  • Jean-Pierre Routy

    (McGill University Heath Centre)

  • Rémi Fromentin

    (Centre de Recherche du Centre Hospitalier de l’Université de Montréal)

  • Nicolas Chomont

    (Université de Montréal
    Centre de Recherche du Centre Hospitalier de l’Université de Montréal)

Abstract

Clonal expansions occur in the persistent HIV reservoir as shown by the duplication of proviral integration sites. However, the source of the proliferation of HIV-infected cells remains unclear. Here, we analyze the TCR repertoire of single HIV-infected cells harboring translation-competent proviruses in longitudinal samples from eight individuals on antiretroviral therapy (ART). When compared to uninfected cells, the TCR repertoire of reservoir cells is heavily biased: expanded clonotypes are present in all individuals, account for the majority of reservoir cells and are often maintained over time on ART. Infected T cell clones are detected at low frequencies in the long-lived central memory compartment and overrepresented in the most differentiated memory subsets. Our results indicate that clonal expansions highly contribute to the persistence of the HIV reservoir and suggest that reservoir cells displaying a differentiated phenotype are the progeny of infected central memory cells undergoing antigen-driven clonal expansion during ART.

Suggested Citation

  • Pierre Gantner & Amélie Pagliuzza & Marion Pardons & Moti Ramgopal & Jean-Pierre Routy & Rémi Fromentin & Nicolas Chomont, 2020. "Single-cell TCR sequencing reveals phenotypically diverse clonally expanded cells harboring inducible HIV proviruses during ART," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17898-8
    DOI: 10.1038/s41467-020-17898-8
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    Cited by:

    1. Caroline Dufour & Corentin Richard & Marion Pardons & Marta Massanella & Antoine Ackaoui & Ben Murrell & Bertrand Routy & Réjean Thomas & Jean-Pierre Routy & Rémi Fromentin & Nicolas Chomont, 2023. "Phenotypic characterization of single CD4+ T cells harboring genetically intact and inducible HIV genomes," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Daniel B. Reeves & Charline Bacchus-Souffan & Mark Fitch & Mohamed Abdel-Mohsen & Rebecca Hoh & Haelee Ahn & Mars Stone & Frederick Hecht & Jeffrey Martin & Steven G. Deeks & Marc K. Hellerstein & Jos, 2023. "Estimating the contribution of CD4 T cell subset proliferation and differentiation to HIV persistence," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. Marion Pardons & Basiel Cole & Laurens Lambrechts & Willem van Snippenberg & Sofie Rutsaert & Ytse Noppe & Nele De Langhe & Annemieke Dhondt & Jerel Vega & Filmon Eyassu & Erik Nijs & Ellen Van Gulck , 2023. "Potent latency reversal by Tat RNA-containing nanoparticle enables multi-omic analysis of the HIV-1 reservoir," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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