HYBRID EVENT: You can participate in person at Rome, Italy or Virtually from your home or work.

2nd Edition of Virology World Conference

21-22, 2023

June 12 -14, 2024 | Rome, Italy
Virology 2022

Olivia Munoz

Speaker at Virology World Conference 2022 - Olivia Munoz
Lausanne University Hospital, Switzerland
Title : Active PD-L1 Incorporation within HIV Virions Functionally Impairs T Follicular Helper cells

Abstract:

Abstract:
The limited development of broadly neutralizing antibodies during the course of 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 functional impairment and the signals contributing to this condition remain elusive Interestingly, Tfh cells express high level of functionally active PD-1, however, in LNs, PD-1 ligands i.e. PD-L1 and PD-L2 are predominantly expressed on cells locating in extrafollicular area. These data suggest that the source of immune checkpoint ligands (IC-Ls) interfering with Tfh cell functionality might not be dependent on the tissue expression of IC-Ls.
We therefore hypothesized that membrane-bound extracellular vesicles such as exosomes and/or HIV virions may incorporate functionally active IC-Ls that may subsequently interfere with Tfh cell functionality.
In the present study, we showed that HIV virions represent the major source (>70%) of PD-L1+ extracellular vesicles as compared to exosomes in plasma of viremic HIV-infected individuals, which translated into a significant increase of soluble plasmatic PD-L1 levels. Furthermore, PD-L1 incorporation within plasmatic HIV virions was more frequently detected than HLA-DR (PD-L1=37.5%; HLA-DR=23.3%), demonstrating the preponderance of this phenomenon in vivo. In addition, we showed that PD-L1 is incorporated within HIV virions during budding processes, through an active mechanism involving p17 HIV matrix protein interactions with the cytoplasmic tail of PD-L1. Using a reconstructive approach, we subsequently showed that in vitro produced PD-L1high but not PD-L1low HIV virions, significantly reduced Tfh cell proliferation and IL-21 production, which ultimately translated into reduced IgG1 production from LN germinal center 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.

What will audience learn from your presentation?

  • First, this study proposes to re-evaluate the role of soluble IC-L in the functional alteration of T cells during HIV infection.
  • Second, this study highlights a novel active mechanism by which HIV exploits a physiological mechanism developed to protect tissues from collateral damages associated with unregulated immune responses.
  • These new observations were made possible by the development of a novel methodology combining the immunocapture of HIV virions and a comprehensive characterization by mass cytometry of host molecules incorporated into HIV virions.

Biography:

Olivia Munoz studied medical biology with a focus on immunology and cancer at the University of Lausanne (Switzerland) and graduated as MS in 2018. She then joined the research group of Prof. Matthieu Perreau at the Services of Immunology and Allergy (IAL) of the Lausanne University Hospital (CHUV) in 2018 to start her PhD working on HIV pathogenesis.

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