Active PD-L1 incorporation within HIV virions functionally impairs T follicular helper cells.

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Version: author
License: CC BY 4.0
Serval ID
serval:BIB_BEB839579791
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Active PD-L1 incorporation within HIV virions functionally impairs T follicular helper cells.
Journal
PLoS pathogens
Author(s)
Munoz O., Banga R., Schelling R., Procopio F.A., Mastrangelo A., Nortier P., Ohmiti K., Daraspe J., Cavassini M., Fenwick C., Perez L., Perreau M.
ISSN
1553-7374 (Electronic)
ISSN-L
1553-7366
Publication state
Published
Issued date
07/2022
Peer-reviewed
Oui
Volume
18
Number
7
Pages
e1010673
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
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.
Keywords
B-Lymphocytes, HIV Infections, Humans, T Follicular Helper Cells, T-Lymphocytes, Helper-Inducer, Virion
Pubmed
Web of science
Open Access
Yes
Create date
12/07/2022 10:10
Last modification date
09/03/2023 6:49
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