Spontaneous HIV expression during suppressive ART is associated with the magnitude and function of HIV-specific CD4+ and CD8+ T cells.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY-NC-ND 4.0
ID Serval
serval:BIB_AFE4FC5A5F3C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Spontaneous HIV expression during suppressive ART is associated with the magnitude and function of HIV-specific CD4+ and CD8+ T cells.
Périodique
Cell host & microbe
Auteur⸱e⸱s
Dubé M., Tastet O., Dufour C., Sannier G., Brassard N., Delgado G.G., Pagliuzza A., Richard C., Nayrac M., Routy J.P., Prat A., Estes J.D., Fromentin R., Chomont N., Kaufmann D.E.
ISSN
1934-6069 (Electronic)
ISSN-L
1931-3128
Statut éditorial
Publié
Date de publication
13/09/2023
Peer-reviewed
Oui
Volume
31
Numéro
9
Pages
1507-1522.e5
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Spontaneous transcription and translation of HIV can persist during suppressive antiretroviral therapy (ART). The quantity, phenotype, and biological relevance of this spontaneously "active" reservoir remain unclear. Using multiplexed single-cell RNAflow-fluorescence in situ hybridization (FISH), we detect active HIV transcription in 14/18 people with HIV on suppressive ART, with a median of 28/million CD4 <sup>+</sup> T cells. While these cells predominantly exhibit abortive transcription, p24-expressing cells are evident in 39% of participants. Phenotypically diverse, active reservoirs are enriched in central memory T cells and CCR6- and activation-marker-expressing cells. The magnitude of the active reservoir positively correlates with total HIV-specific CD4 <sup>+</sup> and CD8 <sup>+</sup> T cell responses and with multiple HIV-specific T cell clusters identified by unsupervised analysis. These associations are particularly strong with p24-expressing active reservoir cells. Single-cell vDNA sequencing shows that active reservoirs are largely dominated by defective proviruses. Our data suggest that these reservoirs maintain HIV-specific CD4 <sup>+</sup> and CD8 <sup>+</sup> T responses during suppressive ART.
Mots-clé
Humans, CD8-Positive T-Lymphocytes, In Situ Hybridization, Fluorescence, Phenotype, Proviruses, CD4-Positive T-Lymphocytes, HIV, HIV-specific CD4 T cell responses, HIV-specific CD8 T cell responses, antiretroviral therapy, flow cytometric fluorescence in situ RNA hybridization, spontaneously active reservoirs, viral reservoirs, viral transcription, viral translation
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/09/2023 17:10
Dernière modification de la notice
24/11/2023 8:14
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