Host cell kinases and the hepatitis C virus life cycle
Host cell kinases and the hepatitis C virus life cycle
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DOI：
10.1016/j.bbapap.2015.04.011
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发表时间：
2015-10-01
影响因子：
3.2
通讯作者：
Baumert, Thomas F.
中科院分区：
文献类型：
--
作者：
Colpitts, Che C.;Lupberger, Joachim;Baumert, Thomas F.
丙型肝炎病毒（HCV）感染依赖于病毒与宿主与人肝细胞的相互作用，在这种情况下，宿主细胞激酶在HCV生命周期的每一步都起着关键作用。在病毒进入过程中，细胞激酶，包括EGFR， EphA2和PICA，调节宿主HCV进入因子的定位并诱导受体复合物组装。在病毒粒子内化之后，病毒基因组在内质网衍生的膜网上复制。膜网的形成取决于HCV NS5a蛋白和PI4KIII α之间的相互作用。受PI4KIII α、CKI等激酶调控的NS5a磷酸化状态，也作为病毒粒子组装的分子开关，发生在脂滴上。HCV激活IKK α可促进脂滴的形成。鉴于病毒生命周期中的多个关键步骤是由宿主细胞激酶介导的，这些酶也代表了抗病毒治疗的互补靶点。这篇文章是题为“蛋白激酶抑制剂”的特刊的一部分。(C) 2015 Elsevier B.V.版权所有
Hepatitis C virus (HCV) infection relies on virus-host interactions with human hepatocytes, a context in which host cell kinases play critical roles in every step of the HCV life cycle. During viral entry, cellular kinases, including EGFR, EphA2 and PICA, regulate the localization of host HCV entry factors and induce receptor complex assembly. Following virion internalization, viral genomes replicate on endoplasmic reticulum-derived membranous webs. The formation of membranous webs depends on interactions between the HCV NS5a protein and PI4KIII alpha. The phosphorylation status of NS5a, regulated by PI4KIII alpha, CKI and other kinases, also acts as a molecular switch to virion assembly, which takes place on lipid droplets. The formation of lipid droplets is enhanced by HCV activation of IKK alpha. In view of the multiple crucial steps in the viral life cycle that are mediated by host cell kinases, these enzymes also represent complementary targets for antiviral therapy. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases. (C) 2015 Elsevier B.V. All rights reserved.