Fusogenic structural changes in arenavirus glycoproteins are associated with viroporin activity.

Autor: Zhang Y; Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, United States of America.; Children's Healthcare of Atlanta, Atlanta, Georgia, United States of America., York J; Montana Biotechnology Center, University of Montana, Missoula, Montana, United States of America., Brindley MA; Department of Infectious Diseases, Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America., Nunberg JH; Montana Biotechnology Center, University of Montana, Missoula, Montana, United States of America., Melikyan GB; Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, United States of America.; Children's Healthcare of Atlanta, Atlanta, Georgia, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2023 Jul 26; Vol. 19 (7), pp. e1011217. Date of Electronic Publication: 2023 Jul 26 (Print Publication: 2023).
DOI: 10.1371/journal.ppat.1011217
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
(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.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje