A fusion peptide in preS1 and the human protein disulfide isomerase ERp57 are involved in hepatitis B virus membrane fusion process

eLife

Floriane Fusil¹  François-Loïc Cosset¹  Rémi Pereira de Oliveira¹  Bertrand Boson¹  Jimena Pérez-Vargas¹  Natalia Freitas¹  Fouzia Amirache¹  Christophe Combet²  Anja Böckmann³  Alessandra Carbone⁴  Elin Teppa⁵ 

[1] CIRI – Centre International de Recherche en Infectiologie, Univ Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS Lyon, Lyon, France;Cancer Research Center of Lyon (CRCL), UMR Inserm 1052 - CNRS 5286 - Université Lyon 1 - Centre Léon Bérard, Lyon, France;Molecular Microbiology and Structural Biochemistry, UMR5086 CNRS-Université Lyon 1, Lyon, France;Sorbonne Université, CNRS, IBPS, Laboratoire de Biologie Computationnelle et Quantitative (LCQB) - UMR 7238, Paris, 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;

关键词: hepatitis B virus;    membrane fusion;    cell entry;    Virus;   

DOI  :  10.7554/eLife.64507

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY