A fusion peptide in preS1 and the human protein-disulfide isomerase ERp57 are involved in HBV membrane fusion process

  1. Jimena Pérez-Vargas
  2. Elin Teppa
  3. Fouzia Amirache
  4. Bertrand Boson
  5. Rémi Pereira de Oliveira
  6. Christophe Combet
  7. Anja Böckmann
  8. Floriane Fusil
  9. Natalia Freitas  Is a corresponding author
  10. Alessandra Carbone  Is a corresponding author
  11. François-Loïc Cosset  Is a corresponding author
  1. École normale supérieure de Lyon, France
  2. Sorbonne Université, France
  3. Centre International de Recherche en Infectiologie, France
  4. Cancer Research Center of Lyon (CRCL), France
  5. University of Lyon, France
  6. Sorbonne Universités, UPMC Univ. Paris 06, France

Abstract

Cell entry of enveloped viruses relies on the fusion between the viral and plasma or endosomal membranes, through a mechanism that is triggered by a cellular signal. Here we used a combination of computational and experimental approaches to unravel the main determinants of hepatitis B virus (HBV) membrane fusion process. We discovered that ERp57 is a host factor critically involved in triggering HBV fusion and infection. Then, through modelling approaches, we uncovered a putative allosteric cross-strand disulfide (CSD) bond in the HBV S glycoprotein and we demonstrate that its stabilization could prevent membrane fusion. Finally, we identified and characterized a potential fusion peptide in the preS1 domain of the HBV L glycoprotein. These results underscore a membrane fusion mechanism that could be triggered by ERp57, allowing a thiol/disulfide exchange reaction to occur and regulate isomerization of a critical CSD, which ultimately leads to the exposition of the fusion peptide.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for figures 1-3, 5-7 and 9.

Article and author information

Author details

  1. Jimena Pérez-Vargas

    École normale supérieure de Lyon, Lyon, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Elin Teppa

    UMR 7238, Biologie Computationnelle et Quantitative, Sorbonne Université, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Fouzia Amirache

    École normale supérieure de Lyon, Lyon, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Bertrand Boson

    Centre International de Recherche en Infectiologie, Lyon, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Rémi Pereira de Oliveira

    École normale supérieure de Lyon, Lyon, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Christophe Combet

    U1052, Cancer Research Center of Lyon (CRCL), Lyon, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7348-3520
  7. Anja Böckmann

    Molecular Microbiology and Structural Biochemistry, University of Lyon, Lyon, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8149-7941
  8. Floriane Fusil

    École normale supérieure de Lyon, Lyon, France
    Competing interests
    The authors declare that no competing interests exist.
  9. Natalia Freitas

    École normale supérieure de Lyon, Lyon, France
    For correspondence
    natalia.bezerra-de-freitas@ens-lyon.fr
    Competing interests
    The authors declare that no competing interests exist.
  10. Alessandra Carbone

    UMR 7238, Biologie Computationnelle et Quantitative, Sorbonne Universités, UPMC Univ. Paris 06, Paris, France
    For correspondence
    Alessandra.Carbone@lip6.fr
    Competing interests
    The authors declare that no competing interests exist.
  11. François-Loïc Cosset

    École normale supérieure de Lyon, Lyon, France
    For correspondence
    flcosset@ens-lyon.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8842-3726

Funding

ANRS (ECTZ160643)

  • François-Loïc Cosset

ANR (ANR-11-LABX-0048)

  • François-Loïc Cosset

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Mark Marsh, University College London, United Kingdom

Ethics

Animal experimentation: All experiments were performed in accordance with the European Union guidelines for approval of the protocols by the local ethics committee (Authorization Agreement C2EA-15, "Comité Rhône-Alpes d'Ethique pour l'Expérimentation Animale", Lyon, France - APAFIS#27316-2020060810332115 v4).

Version history

  1. Received: October 31, 2020
  2. Accepted: June 29, 2021
  3. Accepted Manuscript published: June 30, 2021 (version 1)
  4. Version of Record published: July 15, 2021 (version 2)

Copyright

© 2021, Pérez-Vargas et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Jimena Pérez-Vargas
  2. Elin Teppa
  3. Fouzia Amirache
  4. Bertrand Boson
  5. Rémi Pereira de Oliveira
  6. Christophe Combet
  7. Anja Böckmann
  8. Floriane Fusil
  9. Natalia Freitas
  10. Alessandra Carbone
  11. François-Loïc Cosset
(2021)
A fusion peptide in preS1 and the human protein-disulfide isomerase ERp57 are involved in HBV membrane fusion process
eLife 10:e64507.
https://doi.org/10.7554/eLife.64507

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https://doi.org/10.7554/eLife.64507

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