PKR protein kinase is activated by hepatitis C virus and inhibits viral replication through translational control
PKR protein kinase is activated by hepatitis C virus and inhibits viral replication through translational control
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DOI：
10.1016/j.virusres.2009.01.007
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发表时间：
2009-06-01
期刊：
影响因子：
5
通讯作者：
Ahn, Byung-Yoon
中科院分区：
文献类型：
--
作者：
Kang, Ju-Il;Kwon, Shi-Nae;Ahn, Byung-Yoon
丙型肝炎病毒（HCV）感染目前用基于IFN α的疗法治疗，但IFN α如何抑制HCV复制知之甚少。我们在这里表明，HCV JFH 1感染的人肝癌Huh-7细胞导致IFN诱导蛋白激酶PKR的激活和翻译起始因子eIF 2 α的磷酸化。与对照细胞相比，HCV复制在PKR敲低细胞中显著升高，引起10倍更高的病毒滴度，并且对IFN α处理不太敏感。相反，PKR的瞬时表达以激酶依赖的方式抑制HCV复制，同时增加eIF 2 α磷酸化。此外，磷酸模拟eIF 2 α突变体的表达适度抑制HCV复制。总之，这些结果表明PKR被HCV感染激活，并通过抑制病毒蛋白翻译发挥关键的抗病毒作用。(C)2009爱思唯尔有限公司版权所有。
Hepatitis C virus (HCV) infection is currently treated with IFN alpha-based therapy but little is known how IFN alpha inhibits HCV replication. We show here that HCV JFH1 infection of human hepatoma Huh-7 cells leads to the activation of IFN-inducible protein kinase PKR and phosphorylation of the translation initiation factor eIF2 alpha. Compared to a control cell HCV replication was significantly elevated in a PKR-knockdown cell, giving rise to a 10-fold higher viral titer, and was less sensitive to IFN alpha treatment. Conversely, transient expression of PKR inhibited HCV replication in a kinase-dependent manner with concomitant increase of eIF2 alpha phosphorylation. Further, expression of a phospho-mimetic eIF2 alpha mutant moderately inhibited HCV replication. Together, these results demonstrate that PKR is activated by HCV infection and plays a critical antiviral role through inhibition of viral protein translation. (C) 2009 Elsevier B.V. All rights reserved.