Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Hepatology. 2011 Dec;54(6):1947-55. doi: 10.1002/hep.24610.
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.
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.
丙型肝炎病毒（HCV）是肝硬化和肝细胞癌的主要病因。目前的抗病毒疗法未能清除大量病例的感染。药物开发的重点是非结构蛋白，这些蛋白是 RNA 复制所必需的。接受原位肝移植的个体面临着移植物迅速、普遍的再感染。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，我们发现多酚表没食子儿茶素没食子酸酯（EGCG）是 HCV 进入抑制剂。先前发现绿茶儿茶素，如 EGCG 及其衍生物表儿茶素（EGC）、没食子儿茶素没食子酸酯（ECG）和表儿茶素（EC），具有抗病毒和抗癌特性。EGCG 对 HCV RNA 复制、组装或释放子代病毒颗粒没有影响。然而，它强烈抑制细胞培养衍生的 HCV（HCVcc）进入肝癌细胞系和原代人肝细胞。该效果独立于 HCV 基因型，并且阻断了细胞外病毒粒子的感染和细胞间传播。在 HCV 接种前用 EGCG 预处理细胞不会降低 HCV 感染，而在接种期间应用 EGCG 则强烈抑制 HCV 感染性。此外，在接种期间直接用 EGCG 处理强烈抑制 HCV 感染性。EGCG 不改变所有已知的 HCV（共）受体的表达水平。最后，我们表明 EGCG 抑制病毒与细胞的附着，从而破坏 HCV 细胞进入的初始步骤。
绿茶分子 EGCG 强烈抑制 HCV 进入，可成为旨在预防肝移植后 HCV 再感染的抗病毒策略的一部分。
