Activation of the interferon-inducible protein kinase PKR by Hepatocellular carcinoma derived-Hepatitis C virus core protein
Activation of the interferon-inducible protein kinase PKR by Hepatocellular carcinoma derived-Hepatitis C virus core protein
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DOI：
10.1038/sj.onc.1204744
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发表时间：
2001-09-13
期刊：
影响因子：
8
通讯作者：
Brechot, C
中科院分区：
文献类型：
--
作者：
Delhem, N;Sabile, A;Brechot, C
丙型肝炎病毒（HCV）是慢性肝病和肝细胞癌（HCC）的主要病原体。我们由此证明，HCV核心蛋白编码的序列分离自肝癌肿瘤组织，但不是那些来自它们的非肿瘤对应物在同一个肝脏，共定位在体外和体内和共免疫沉淀PKR在肝细胞Huh 7细胞。我们发现，这种关联实际上增加了PKR的自磷酸化和翻译起始因子eIF 2 α的磷酸化，这是PKR活性的两个标志物。因此，本研究确定了一种新的病毒-细胞相互作用模型，其中病毒蛋白，HCV核心，激活PKR活性。
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.