A fusion peptide in preS1 and the human protein disulfide isomerase ERp57 are involved in hepatitis B virus membrane fusion process
Jimena Pérez-Vargas,
Elin Teppa,
Fouzia Amirache,
Bertrand Boson,
Rémi Pereira de Oliveira,
Christophe Combet,
Anja Böckmann,
Floriane Fusil,
Natalia Freitas,
Alessandra Carbone,
François-Loïc Cosset
Affiliations
Jimena Pérez-Vargas
CIRI – Centre International de Recherche en Infectiologie, Univ Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS Lyon, Lyon, France
Sorbonne Université, CNRS, IBPS, Laboratoire de Biologie Computationnelle et Quantitative (LCQB) - UMR 7238, Paris, France; Sorbonne Université, Institut des Sciences du Calcul et des Données (ISCD), Paris, France
CIRI – Centre International de Recherche en Infectiologie, Univ Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS Lyon, Lyon, France
CIRI – Centre International de Recherche en Infectiologie, Univ Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS Lyon, Lyon, France
CIRI – Centre International de Recherche en Infectiologie, Univ Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS Lyon, Lyon, France
Molecular Microbiology and Structural Biochemistry, UMR5086 CNRS-Université Lyon 1, Lyon, France
Floriane Fusil
CIRI – Centre International de Recherche en Infectiologie, Univ Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS Lyon, Lyon, France
CIRI – Centre International de Recherche en Infectiologie, Univ Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS Lyon, Lyon, France
CIRI – Centre International de Recherche en Infectiologie, Univ Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS Lyon, Lyon, France
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 modeling 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.