Fiche publication
Date publication
mai 2017
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BAUMERT Thomas
Tous les auteurs :
Haqshenas G, Wu J, Simpson KJ, Daly RJ, Netter HJ, Baumert TF, Doerig C
Lien Pubmed
Résumé
Host cell signalling during infection with intracellular pathogens remains poorly understood. Here we report on the use of antibody microarray technology to detect variations in the expression levels and phosphorylation status of host cell signalling proteins during hepatitis C virus (HCV) replication. Following transfection with HCV RNA, the JNK and NF-κB pathways are suppressed, while the JAK/STAT5 pathway is activated; furthermore, components of the apoptosis and cell cycle control machineries are affected in the expression and/or phosphorylation status. RNAi-based hit validation identifies components of the JAK/STAT, NF-κB, MAPK and calcium-induced pathways as modulators of HCV replication. Selective chemical inhibition of one of the identified targets, the JNK activator kinase MAP4K2, does impair HCV replication. Thus this study provides a comprehensive picture of host cell pathway mobilization by HCV and uncovers potential therapeutic targets. The strategy of identifying targets for anti-infective intervention within the host cell signalome can be applied to any intracellular pathogen.
Mots clés
Hepacivirus, genetics, Hepatitis C, genetics, Host-Pathogen Interactions, Humans, Janus Kinases, genetics, NF-kappa B, genetics, Phosphorylation, STAT5 Transcription Factor, genetics, Signal Transduction, Virus Replication
Référence
Nat Commun. 2017 May 8;8:15158
