Titre
Sex and Age Impact CD4+ T Cell Susceptibility to HIV In Vitro through Cell Activation Dynamics.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Brandt, L.
Auteure/Auteur
Angelino, P.
Auteure/Auteur
Martinez, R.
Auteure/Auteur
Cristinelli, S.
Auteure/Auteur
Ciuffi, A.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
2073-4409
Statut éditorial
Publié
Date de publication
2023-11-23
Volume
12
Numéro
23
Première page
2689
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Résumé
Cellular composition and the responsiveness of the immune system evolve upon aging and are influenced by biological sex. CD4+ T cells from women living with HIV exhibit a decreased viral replication ex vivo compared to men's. We, thus, hypothesized that these findings could be recapitulated in vitro and infected primary CD4+ T cells with HIV-based vectors pseudotyped with VSV-G or HIV envelopes. We used cells isolated from twenty donors to interrogate the effect of sex and age on permissiveness over a six-day activation kinetics. Our data identified an increased permissiveness to HIV between 24 and 72 h post-stimulation. Sex- and age-based analyses at these time points showed an increased susceptibility to HIV of the cells isolated from males and from donors over 50 years of age, respectively. A parallel assessment of surface markers' expression revealed higher frequencies of activation marker CD69 and of immune checkpoint inhibitors (PD-1 and CTLA-4) in the cells from highly permissive donors. Furthermore, positive correlations were identified between the expression kinetics of CD69, PD-1 and CTLA-4 and HIV expression kinetics. The cell population heterogeneity was assessed using a single-cell RNA-Seq analysis and no cell subtype enrichment was identified according to sex. Finally, transcriptomic analyses further highlighted the role of activation in those differences with enriched activation and cell cycle gene sets in male and older female cells. Altogether, this study brought further evidence about the individual features affecting HIV replication at the cellular level and should be considered in latency reactivation studies for an HIV cure.
PID Serval
serval:BIB_475AE3709556
PMID
Open Access
Oui
Date de création
2023-11-27T09:56:43.706Z
Date de création dans IRIS
2025-05-20T13:42:07Z
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Nom
cells-12-02689-v2.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by/4.0
Taille
4.17 MB
Format
Adobe PDF
PID Serval
serval:BIB_475AE3709556.P001
URN
urn:nbn:ch:serval-BIB_475AE37095561
Somme de contrôle
(MD5):88b0a8a53967360e0f3504b761b7bf6b