Expression of hepatitis C virus proteins inhibits signal transduction through the Jak-STAT pathway

Détails

ID Serval
serval:BIB_D52D89C000F2
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Expression of hepatitis C virus proteins inhibits signal transduction through the Jak-STAT pathway
Périodique
Journal of Virology
Auteur(s)
Heim  M. H., Moradpour  D., Blum  H. E.
ISSN
0022-538X (Print)
Statut éditorial
Publié
Date de publication
10/1999
Volume
73
Numéro
10
Pages
8469-75
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Oct
Résumé
Hepatitis C virus (HCV) infection is a leading cause of liver disease worldwide. Alpha interferon (IFN-alpha) therapy of chronic hepatitis C leads to a sustained response in 10 to 20% of patients only. The mechanisms of viral persistence and the pathogenesis of hepatitis C are poorly understood. We established continuous human cell lines, allowing the tightly regulated expression of the entire HCV open reading frame under the control of a tetracycline-responsive promoter. Using this in vitro system, we analyzed the effect of HCV proteins on IFN-induced intracellular signaling. Expression of HCV proteins in these cells strongly inhibited IFN-alpha-induced signal transduction through the Jak-STAT pathway. Inhibition occurred downstream of STAT tyrosine phosphorylation. Inhibition of the Jak-STAT pathway was not restricted to IFN-alpha-induced signaling but was observed in leukemia inhibitory factor-induced signaling through Stat3 as well. By contrast, tumor necrosis factor alpha-induced activation of the transcription factor NF-kappaB was not affected. Interference of HCV with IFN-alpha-induced signaling through the Jak-STAT pathway could contribute to the resistance to IFN-alpha therapy observed in the majority of patients and may represent a general escape strategy of HCV contributing to viral persistence and pathogenesis of chronic liver disease.
Mots-clé
Antiviral Agents/pharmacology/therapeutic use Cell Line DNA-Binding Proteins/metabolism Hepacivirus/*physiology Hepatitis C/drug therapy/metabolism/*virology Humans Interferon-alpha/pharmacology/therapeutic use NF-kappa B/metabolism Protein-Tyrosine Kinases/metabolism STAT1 Transcription Factor *Signal Transduction Trans-Activators/metabolism Viral Proteins/*biosynthesis Virus Replication
Pubmed
Web of science
Création de la notice
25/01/2008 16:06
Dernière modification de la notice
20/08/2019 15:55
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