A fusion peptide in preS1 and the human protein disulfide isomerase ERp57 are involved in hepatitis B virus membrane fusion process.
Animals
CHO Cells
Cell Line, Tumor
Cricetinae
Cricetulus
Female
Gene Expression Regulation, Viral
Hepatitis B Surface Antigens
/ metabolism
Hepatitis B virus
Hepatocytes
Humans
Male
Membrane Fusion
Mice
Protein Disulfide-Isomerases
/ genetics
Protein Precursors
/ metabolism
Viral Envelope Proteins
/ genetics
Virus Attachment
cell entry
computational biology
hepatitis B virus
infectious disease
membrane fusion
microbiology
systems biology
virus
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
30 06 2021
30 06 2021
Historique:
received:
31
10
2020
accepted:
29
06
2021
pubmed:
1
7
2021
medline:
21
10
2021
entrez:
30
6
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34190687
doi: 10.7554/eLife.64507
pii: 64507
pmc: PMC8282342
doi:
pii:
Substances chimiques
Hepatitis B Surface Antigens
0
Protein Precursors
0
Viral Envelope Proteins
0
presurface protein 1, hepatitis B surface antigen
0
Protein Disulfide-Isomerases
EC 5.3.4.1
PDIA3 protein, human
EC 5.3.4.1.
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2021, Pérez-Vargas et al.
Déclaration de conflit d'intérêts
JP, ET, FA, BB, RP, CC, AB, FF, NF, AC, FC No competing interests declared
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