The Green Tea Polyphenol, Epigallocatechin-3-Gallate, Inhibits Hepatitis C Virus Entry
The Green Tea Polyphenol, Epigallocatechin-3-Gallate, Inhibits Hepatitis C Virus Entry
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DOI：
10.1002/hep.24610
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发表时间：
2011-12-01
期刊：
影响因子：
13.5
通讯作者：
Steinmann, Eike
中科院分区：
文献类型：
--
作者：
Ciesek, Sandra;von Hahn, Thomas;Steinmann, Eike
丙型肝炎病毒（HCV）是导致肝硬化和肝细胞癌的主要原因。目前的抗病毒治疗在相当大比例的病例中未能清除感染。药物开发的重点是RNA复制所需的非结构蛋白。接受原位肝移植的个体面临移植物的快速、普遍再感染。因此，迫切需要针对感染早期阶段的抗病毒策略来预防HCV感染。在这项研究中，我们确定了多酚，表没食子儿茶素-3-没食子酸酯（EGCG），作为HCV进入的抑制剂。绿色茶儿茶素，如表没食子儿茶素及其衍生物、表没食子儿茶素（EGC）、表儿茶素没食子酸酯（ECG）和表儿茶素（EC），先前已被发现发挥抗病毒和抗癌特性。表没食子儿茶素没食子酸酯对HCV RNA复制、装配或子代病毒体释放没有影响。然而，它有效地抑制细胞培养衍生的HCV（HCV-HCV）进入肝癌细胞系以及原代人肝细胞。这种效应与HCV基因型无关，细胞外病毒粒子对细胞的感染和细胞间传播均被阻断。在HCV接种前用EGCG预处理细胞并不能减少HCV感染，而在接种过程中应用EGCG强烈抑制HCV感染。此外，在接种期间直接用EGCG处理强烈抑制HCV感染性。所有已知的HCV（共）受体的表达水平均未被EGCG改变。最后，我们发现EGCG抑制病毒附着到细胞上，从而破坏HCV进入细胞的初始步骤。结论：绿色茶分子，表没食子儿茶素没食子酸酯，有效地抑制丙型肝炎病毒的进入，并可能成为旨在预防肝移植后丙型肝炎病毒再感染的抗病毒策略的一部分。（肝脏学2011; 54：1947-1955）
Hepatitis C virus (HCV) is a major cause of liver cirrhosis and hepatocellular carcinoma. Current antiviral therapy fails to clear infection in a substantial proportion of cases. Drug development is focused on nonstructural proteins required for RNA replication. Individuals undergoing orthotopic liver transplantation face rapid, universal reinfection of the graft. Therefore, antiviral strategies targeting the early stages of infection are urgently needed for the prevention of HCV infection. In this study, we identified the polyphenol, epigallocatechin-3-gallate (EGCG), as an inhibitor of HCV entry. Green tea catechins, such as EGCG and its derivatives, epigallocatechin (EGC), epicatechin gallate (ECG), and epicatechin (EC), have been previously found to exert antiviral and antioncogenic properties. EGCG had no effect on HCV RNA replication, assembly, or release of progeny virions. However, it potently inhibited Cell-culture-derived HCV (HCVcc) entry into hepatoma cell lines as well as primary human hepatocytes. The effect was independent of the HCV genotype, and both infection of cells by extracellular virions and cell-to-cell spread were blocked. Pretreatment of cells with EGCG before HCV inoculation did not reduce HCV infection, whereas the application of EGCG during inoculation strongly inhibited HCV infectivity. Moreover, treatment with EGCG directly during inoculation strongly inhibited HCV infectivity. Expression levels of all known HCV (co-) receptors were unaltered by EGCG. Finally, we showed that EGCG inhibits viral attachment to the cell, thus disrupting the initial step of HCV cell entry. Conclusion: The green tea molecule, EGCG, potently inhibits HCV entry and could be part of an antiviral strategy aimed at the prevention of HCV reinfection after liver transplantation. (HEPATOLOGY 2011; 54: 1947-1955)