Journal article
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, Christian Doerig
NATURE COMMUNICATIONS | NATURE PUBLISHING GROUP | Published : 2017
DOI: 10.1038/ncomms15158
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 replicati..
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Awarded by NIH
Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Funding Acknowledgements
We thank Professor Charles Rice for providing us with HCV full genome cDNA constructs and antibodies to NS5A. We thank Professor Francis Chisari for the Huh7.5.1 human hepatoma cell line. We thank Professor Nathan Gray and Dr Tan Li (Harvard University) for the TL4-12 compound. We thank Dr Brendan Russ for his assistance with the performance of qRT-PCR. We thank Professor Ralf Bartenschlager (Heidelberg University, Germany) for assisting with control siRNA. Also, we thank Ms Judy Callaghan, the Monash Micro Imaging facility, for their assistance with confocal microscopy. The Victorian Centre for Functional Genomics (K.J.S.) was funded by the Australian Cancer Research Foundation (ACRF), the Victorian Department of Industry, Innovation and Regional Development (DIIRD), the Australian Phenomics Network (APN) and supported by funding from the Australian Government's Education Investment Fund through the Super Science Initiative, the Australasian Genomics Technologies Association (AGTA), the Brockhoff Foundation and the Peter MacCallum Cancer Centre Foundation. T.F.B. acknowledges grant support of the EU (ERC HEPCAR and H2020 HEPCENT) and NIH (U19-AI123862). This work was made possible through a grant from the Australian Centre for HIV and Hepatitis Virology Research (ACH2).