Journal article
A functional genomic screen reveals novel host genes that mediate interferon-alpha's effects against hepatitis C virus
H Zhao, W Lin, K Kumthip, D Cheng, DN Fusco, O Hofmann, N Jilg, AW Tai, K Goto, L Zhang, W Hide, JY Jang, LF Peng, RT Chung
Journal of Hepatology | ELSEVIER | Published : 2012
Abstract
Background & Aims: The precise mechanisms by which IFN exerts its antiviral effect against HCV have not yet been elucidated. We sought to identify host genes that mediate the antiviral effect of IFN-α by conducting a whole-genome siRNA library screen. Methods: High throughput screening was performed using an HCV genotype 1b replicon, pRep-Feo. Those pools with replicate robust Z scores ≥2.0 entered secondary validation in full-length OR6 replicon cells. Huh7.5.1 cells infected with JFH1 were then used to validate the rescue efficacy of selected genes for HCV replication under IFN-α treatment. Results: We identified and confirmed 93 human genes involved in the IFN-α anti-HCV effect using a wh..
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Awarded by National Institutes of Health
Funding Acknowledgements
[ "This work was supported by grants from The National Natural Science Foundation of China (81170386), research foundation of Peking University First Hospital, and the Chinese Scholarship Council (to H.Z.), NIH-MGH Center for Human Immunology Pilot/Feasibility Study Grant (to W.L.), Grants A1082630, and DK078772 (to R.T.C.) from the National Institutes of Health, and U54 A1057159 from NERCE (to R.T.C.), Grant UL1 RR 025758 (to O.H.), and Grant DK088951 from the National Institutes of Health (to L.F.P.).", "We thank Drs. Nobuyuki Kato and Masanori Ikeda for the gift of the OR6 cell line; Dr. Francis Chisari for the Huh7.5.1 cell line; Dr. Takaji Wakita for the infectious HCV virus JFH1 DNA construct. The SART1 overexpression plasmid was obtained from Prof. Mei Yee Koh (Department of Experimental Therapeutics, M.D. Anderson Cancer Center, Houston, Texas). We would like to acknowledge the superb technical assistance provided by Dr. Caroline Shamu, Su Chiang, Tao Ren, Sean Johnston, Stewart Rudnicki, David Wrobel, and Jen Nale at the ICCB-Longwood screening facility at the Harvard Medical School. The project described was conducted with the support of Harvard Catalyst (The Harvard Clinical and Translational Science Center) (NIH award #UL1 RR 025758 and financial contributions from participating institutions). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health." ]