PI4K-beta and MKNK1 are regulators of hepatitis C virus IRES-dependent translation.
PI4K-beta and MKNK1 are regulators of hepatitis C virus IRES-dependent translation.
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DOI：
10.1038/srep13344
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发表时间：
2015-09-01
影响因子：
4.6
通讯作者：
Thoma C
中科院分区：
文献类型：
--
作者：
Lupberger J;Casanova C;Fischer B;Weiss A;Fofana I;Fontaine N;Fujiwara T;Renaud M;Kopp A;Schuster C;Brino L;Baumert TF;Thoma C
细胞翻译受到宿主抗病毒反应的下调。小核糖核酸病毒科和黄病毒科，包括丙型肝炎病毒 (HCV) 使用内部核糖体进入序列 (IRES) 逃避此过程。尽管 HCV IRES 翻译是 HCV 复制的先决条件，但对 IRES 活性至关重要的宿主因素仅有少数已知，并且全球调节网络仍然很大程度上未知。由于信号转导是病毒感染和宿主抗病毒反应的重要调节因子，因此我们将针对人类信号网络的功能性 RNAi 筛选与 HCV IRES 特异性报告基因 mRNA 测定相结合。我们证明HCV宿主细胞辅因子PI4K和MKNK1是HCV IRES翻译的正调节因子，代表了一条与HCV生命周期和IRES介导的病毒RNA翻译具有功能相关性的新途径。
Cellular translation is down-regulated by host antiviral responses. Picornaviridae and Flaviviridae including hepatitis C virus (HCV) evade this process using internal ribosomal entry sequences (IRESs). Although HCV IRES translation is a prerequisite for HCV replication, only few host factors critical for IRES activity are known and the global regulator network remains largely unknown. Since signal transduction is an import regulator of viral infections and the host antiviral response we combined a functional RNAi screen targeting the human signaling network with a HCV IRES-specific reporter mRNA assay. We demonstrate that the HCV host cell cofactors PI4K and MKNK1 are positive regulators of HCV IRES translation representing a novel pathway with a functional relevance for the HCV life cycle and IRES-mediated translation of viral RNA.