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

Journal article

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

Authors: Munoz, O; Banga, R; Schelling, R; Procopio, FA; Mastrangelo, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Public Library of Science
• Journal: PLoS Pathogens
• Volume: 18
• Issue: 7
• Pages: e1010673-e1010673
• Publication date: 2022-07-05
• DOI: 10.1371/journal.ppat.1010673
• EISSN: 1553-7374
• ISSN: 1553-7366
• Language: English
• Keywords: Secretion; In vitro; Virology; Genetics; Biochemistry; Immune system; Cell; Chemistry; Antibody; Follicular phase; Cell biology; Human immunodeficiency virus (HIV); Biology; T cell; Immunology