Phenotypic characterization of single CD4+ T cells harboring genetically intact and inducible HIV genomes

Caroline Dufour, Corentin Richard, Marion Pardons, Marta Massanella, Antoine Ackaoui, Ben Murrell, Bertrand Routy, Réjean Thomas, Jean-Pierre Routy, Rémi Fromentin and Nicolas Chomont ()
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Caroline Dufour: Université de Montréal
Corentin Richard: Université de Montréal
Marion Pardons: Université de Montréal
Marta Massanella: Université de Montréal
Antoine Ackaoui: Université de Montréal
Ben Murrell: Karolinska Institutet
Bertrand Routy: Université de Montréal
Réjean Thomas: Clinique médicale l’Actuel
Jean-Pierre Routy: McGill University Health Centre
Rémi Fromentin: Université de Montréal
Nicolas Chomont: Université de Montréal

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract The phenotype of the rare HIV-infected cells persisting during antiretroviral therapies (ART) remains elusive. We developed a single-cell approach that combines the phenotypic analysis of HIV-infected cells with near full-length sequencing of their associated proviruses to characterize the viral reservoir in 6 male individuals on suppressive ART. We show that individual cells carrying clonally expanded identical proviruses display very diverse phenotypes, indicating that cellular proliferation contributes to the phenotypic diversification of the HIV reservoir. Unlike most viral genomes persisting on ART, inducible and translation-competent proviruses rarely present large deletions but are enriched in defects in the Ψ locus. Interestingly, the few cells harboring genetically intact and inducible viral genomes express higher levels of the integrin VLA-4 compared to uninfected cells or cells with defective proviruses. Viral outgrowth assay confirmed that memory CD4+ T cells expressing high levels of VLA-4 are highly enriched in replication-competent HIV (27-fold enrichment). We conclude that although clonal expansions diversify the phenotype of HIV reservoir cells, CD4+ T cells harboring replication-competent HIV retain VLA-4 expression.

Date: 2023
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36772-x

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DOI: 10.1038/s41467-023-36772-x

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