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Activation of the interferon-inducible protein kinase PKR by Hepatocellular carcinoma derived-Hepatitis C virus core protein

Oncogene volume 20, pages 5836–5845 (2001)Cite this article

Abstract

Hepatitis C virus (HCV) is a major etiological agent of chronic liver disease and hepatocellular carcinoma (HCC). We demonstrate herewith that HCV core proteins encoded by sequences isolated from HCC tumor tissues, but not those derived from their non-tumor counterparts in the same liver, co-localise in vitro and in vivo and co-immunoprecipitate with PKR in hepatocytic Huh7 cells. We show that this association in fact augments the autophosphorylation of PKR and the phosphorylation of the translation initiation factor eIF2α, which are two markers of PKR activity. The present study therefore identifies a novel model of virus-cell interactions whereby a viral protein, the HCV core, activates PKR activity.

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Abbreviations

CHX: Cycloheximide:

HCV: Hepatitis C Virus, IFNα: Interferon alpha, PKR: double-stranded RNA-dependent protein kinase, TNFα: Tumor Necrosis Factor

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Acknowledgements

We thank Y Gourreau, Y Chretien, Dr JP Kolb, Dr MJ Masse and Dr J Wietzerbin for their support.

Author information

Author notes

  1. Rodrigo Gajardo

    Present address: Department of Viral Investigation, Desarollo Institut, Grifols, Spain

  2. Philippe Podevin

    Present address: Department of Hepato-gastroenterology Saint-Antoine hospital, Paris, France

  3. Abdelmajid Sabile, Rodrigo Gajardo and Philippe Podevin: A Sabile, R Gajardo and P Podevin contributed equally to this work

Authors and Affiliations

  1. Department of Liver Cancer and Molecular Virology Inserm U370 CHU Necker, Paris, France

    Nadvia Delhem, Abdelmajid Sabile, Rodrigo Gajardo, Philippe Podevin, Maria Agnes Blaton, Dina Kremsdorf & Christian Brechot

  2. Department of Cytokines and Interferon, Ann Arbor, MI 48109, Michigan, USA

    Annie Abadie

  3. Curie Institute, Paris, France

    Annie Abadie

  4. Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, Michigan, USA

    Laura Beretta

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  1. Nadvia Delhem
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Correspondence to Christian Brechot.

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Delhem, N., Sabile, A., Gajardo, R. et al. Activation of the interferon-inducible protein kinase PKR by Hepatocellular carcinoma derived-Hepatitis C virus core protein. Oncogene 20, 5836–5845 (2001). https://doi.org/10.1038/sj.onc.1204744

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