eLife (Jun 2021)

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

DOI
https://doi.org/10.7554/eLife.64507
Journal volume & issue
Vol. 10

Abstract

Read online

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.

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