Fusogenic structural changes in arenavirus glycoproteins are associated with viroporin activity.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
received:
17
02
2023
accepted:
04
07
2023
revised:
07
08
2023
medline:
8
8
2023
pubmed:
26
7
2023
entrez:
26
7
2023
Statut:
epublish
Résumé
Many enveloped viruses enter host cells by fusing with acidic endosomes. The fusion activity of multiple viral envelope glycoproteins does not generally affect viral membrane permeability. However, fusion induced by the Lassa virus (LASV) glycoprotein complex (GPc) is always preceded by an increase in viral membrane permeability and the ensuing acidification of the virion interior. Here, systematic investigation of this LASV fusion phenotype using single pseudovirus tracking in live cells reveals that the change in membrane barrier function is associated with the fusogenic conformational reorganization of GPc. We show that a small-molecule fusion inhibitor or mutations that impair viral fusion by interfering with GPc refolding into the post-fusion structure prevent the increase in membrane permeability. We find that the increase in virion membrane permeability occurs early during endosomal maturation and is facilitated by virus-cell contact. This increase is observed using diverse arenavirus glycoproteins, whether presented on lentivirus-based pseudoviruses or arenavirus-like particles, and in multiple different cell types. Collectively, these results suggest that conformational changes in GPc triggered by low pH and cell factor binding are responsible for virion membrane permeabilization and acidification of the virion core prior to fusion. We propose that this viroporin-like activity may augment viral fusion and/or post-fusion steps of infection, including ribonucleoprotein release into the cytoplasm.
Identifiants
pubmed: 37494374
doi: 10.1371/journal.ppat.1011217
pii: PPATHOGENS-D-23-00309
pmc: PMC10406333
doi:
Substances chimiques
Viroporin Proteins
0
Glycoproteins
0
Viral Envelope Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1011217Subventions
Organisme : NIAID NIH HHS
ID : R01 AI053668
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI139238
Pays : United States
Informations de copyright
Copyright: © 2023 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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