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

被引:64
作者
Delhem, N
Sabile, A
Gajardo, R
Podevin, P
Abadie, A
Blaton, MA
Kremsdorf, D
Beretta, L
Brechot, C
机构
[1] CHU Necker, INSERM, U370, Dept Liver Canc & Mol Virol, F-75015 Paris, France
[2] Inst Curie, Dept Cytokines & Interferon, Paris, France
[3] Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA
关键词
HCV; core; PKR; eIF2; alpha; apoptosis;
D O I
10.1038/sj.onc.1204744
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 eIF2 alpha, 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.
引用
收藏
页码:5836 / 5845
页数:10
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