Glycogen Synthase Kinase 3β Enhances Hepatitis C Virus Replication by Supporting miR-122.

Détails

ID Serval
serval:BIB_8AC992CA3727
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Glycogen Synthase Kinase 3β Enhances Hepatitis C Virus Replication by Supporting miR-122.
Périodique
Frontiers in microbiology
Auteur(s)
Saleh M., Rüschenbaum S., Welsch C., Zeuzem S., Moradpour D., Gouttenoire J., Lange C.M.
ISSN
1664-302X (Print)
ISSN-L
1664-302X
Statut éditorial
Publié
Date de publication
2018
Peer-reviewed
Oui
Volume
9
Pages
2949
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
Hepatitis C virus (HCV) infection is associated with alterations in host lipid and insulin signaling cascades, which are partially explained by a dependence of the HCV life cycle on key molecules in these metabolic pathways. Yet, little is known on the role in the HCV life cycle of glycogen synthase kinase 3 (GSK3), one of the most important kinases in cellular metabolism. Therefore, the impact of GSK3 on the HCV life cycle was assessed in human hepatoma cell lines harboring subgenomic genotype 1b and 2a replicons or producing cell culture-derived HCV genotype 2a by exposure to synthetic GSK3 inhibitors, GSK3 gene silencing, overexpression of GSK3 constructs and immunofluorescence analyses. In addition, the role of GSK3 in hepatitis E virus (HEV) replication was investigated to assess virus specificity of the observed findings. We found that both inhibition of GSK3 function by synthetic inhibitors as well as silencing of GSK3β gene expression resulted in a decrease of HCV replication and infectious particle production, whereas silencing of the GSK3α isoform had no relevant effect on the HCV life cycle. Conversely, overexpression of GSK3β resulted in enhanced HCV replication. In contrast, GSK3β had no effect on replication of subgenomic HEV replicon. The pro-viral effect of GSK3β on HCV replication was mediated by supporting expression of microRNA-122 (miR-122), a micro-RNA which is mandatory for wild-type HCV replication, as GSK3 inhibitors suppressed miR-122 levels and as inhibitors of GSK3 had no antiviral effect on a miR-122-independent HCV mutant. In conclusion, we have identified GSK3β is a novel host factor supporting HCV replication by maintaining high levels of hepatic miR-122 expression.
Mots-clé
Microbiology (medical), Microbiology, GSK3α, GSK3β, hepatitis E virus, host-targeting antivirals, insulin resistance, miR-122
Pubmed
Web of science
Open Access
Oui
Création de la notice
10/12/2018 18:55
Dernière modification de la notice
20/08/2019 15:49
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