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

Gholamreza Haqshenas (), Jianmin Wu, Kaylene J. Simpson, Roger J. Daly, Hans J. Netter, Thomas F. Baumert and Christian Doerig ()
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Gholamreza Haqshenas: Infection & Immunity Program, Monash University
Jianmin Wu: Garvan Institute of Medical Research
Kaylene J. Simpson: Victorian Centre for Functional Genomics, The Peter MacCallum Cancer Centre
Roger J. Daly: Cancer Program, Monash University
Hans J. Netter: Infection & Immunity Program, Monash University
Thomas F. Baumert: Inserm U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Université de Strasbourg
Christian Doerig: Infection & Immunity Program, Monash University

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: 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-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.

Date: 2017
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DOI: 10.1038/ncomms15158

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