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Signalome-wide assessment of host cell response to hepatitis C virus

Abstract

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-kappaB 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-kappaB, 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.

Type Journal
ISBN 2041-1723 (Electronic) 2041-1723 (Linking)
Authors Haqshenas, G.; Wu, J.; Simpson, K. J.; Daly, R. J.; Netter, H. J.; Baumert, T. F.; Doerig, C.
Responsible Garvan Author Dr Jianmin Wu
Publisher Name Nature Communications
Published Date 2017-05-08
Published Volume 8
Published Pages 15158
Status Published in-print
DOI 10.1038/ncomms15158
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/28480889