Active PD-L1 incorporation within HIV virions functionally impairs T follicular helper cells.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
received:
03
02
2022
accepted:
14
06
2022
revised:
15
07
2022
pubmed:
6
7
2022
medline:
20
7
2022
entrez:
5
7
2022
Statut:
epublish
Résumé
The limited development of broadly neutralizing antibodies (BnAbs) during HIV infection is classically attributed to an inadequate B-cell help brought by functionally impaired T follicular helper (Tfh) cells. However, the determinants of Tfh-cell functional impairment and the signals contributing to this condition remain elusive. In the present study, we showed that PD-L1 is incorporated within HIV virions through an active mechanism involving p17 HIV matrix protein. We subsequently showed that in vitro produced PD-L1high but not PD-L1low HIV virions, significantly reduced Tfh-cell proliferation and IL-21 production, ultimately leading to a decreased of IgG1 secretion from GC B cells. Interestingly, Tfh-cell functions were fully restored in presence of anti-PD-L1/2 blocking mAbs treatment, demonstrating that the incorporated PD-L1 proteins were functionally active. Taken together, the present study unveils an immunovirological mechanism by which HIV specifically exploits the regulatory potential of PD-L1 to suppress the immune system during the course of HIV infection.
Identifiants
pubmed: 35788752
doi: 10.1371/journal.ppat.1010673
pii: PPATHOGENS-D-22-00210
pmc: PMC9286290
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1010673Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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