A fusion peptide in preS1 and the human protein-disulfide isomerase ERp57 are involved in HBV membrane fusion process
- École normale supérieure de Lyon, France
- Sorbonne Université, France
- Centre International de Recherche en Infectiologie, France
- Cancer Research Center of Lyon (CRCL), France
- University of Lyon, France
- 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
François-Loïc Cosset
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.
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).
Reviewing Editor
- Mark Marsh, University College London, United Kingdom
Publication history
- Received: October 31, 2020
- Accepted: June 29, 2021
- Accepted Manuscript published: June 30, 2021 (version 1)
- 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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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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