Role of the host cell's unfolded protein response in arenavirus infection.

Détails

ID Serval
serval:BIB_3BF7CDCB32A5
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Role of the host cell's unfolded protein response in arenavirus infection.
Périodique
Journal of Virology
Auteur(s)
Pasqual G., Burri D.J., Pasquato A., de la Torre J.C., Kunz S.
ISSN
1098-5514 (Electronic)
ISSN-L
0022-538X
Statut éditorial
Publié
Date de publication
2011
Volume
85
Numéro
4
Pages
1662-1670
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Résumé
Arenaviruses are enveloped RNA viruses with a nonlytic life cycle that cause acute and persistent infections. Here, we investigated the role of the host cell's unfolded protein response (UPR) in infection of the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV). In mammalian cells, the endoplasmic reticulum (ER) chaperone protein GRP78/BiP functions as the principal sensor for the induction of the UPR and interacts with three mediators: kinase/endonuclease inositol-requiring protein 1 (IRE1), PKR-like ER kinase (PERK), and activating transcription factor 6 (ATF6). Acute infection with LCMV resulted in a selective induction of the ATF6-regulated branch of the UPR, whereas pathways controlled by PERK and IRE1 were neither activated nor blocked. Expression of individual LCMV proteins revealed that the viral glycoprotein precursor (GPC), but not that of other viral proteins, was responsible for the induction of ATF6. Rapid downregulation of the viral GPC during transition from acute to persistent LCMV infection restored basal levels of UPR signaling. To address a possible role of ATF6 signaling in LCMV infection, we used cells deficient in site 2 protease (S2P), a metalloprotease required for the activation of ATF6. Cells deficient in S2P showed significantly lower levels of production of infectious virus during acute but not persistent infection, indicating a requirement for ATF6-mediated signaling for optimal virus multiplication. In summary, acute LCMV infection seems to selectively induce the ATF6-regulated branch of the UPR that is likely beneficial for virus replication and cell viability, but it avoids induction of PERK and IRE1, whose activation may be detrimental for virus and the host cell.
Mots-clé
Activating Transcription Factor 6/metabolism, Activating Transcription Factor 6/pharmacology, Animals, Arenavirus/pathogenicity, Cell Line, Cell Line, Tumor, Cricetinae, Endoplasmic Reticulum/metabolism, Epithelial Cells/virology, Gene Expression Regulation, Glycoproteins/metabolism, Glycoproteins/pharmacology, Heat-Shock Proteins/metabolism, Humans, Liver/cytology, Liver/virology, Lung/cytology, Lung/virology, Lymphocytic choriomeningitis virus/metabolism, Lymphocytic choriomeningitis virus/pathogenicity, Protein Folding, Protein Precursors/metabolism, Protein Precursors/pharmacology, Signal Transduction, Unfolded Protein Response/drug effects, Unfolded Protein Response/physiology, Viral Envelope Proteins/metabolism, Viral Envelope Proteins/pharmacology
Pubmed
Web of science
Open Access
Oui
Création de la notice
20/03/2011 20:45
Dernière modification de la notice
20/08/2019 14:32
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