德国汉诺威大学 绿茶多酚抑制丙型肝炎病毒进入肝细胞

The green tea polyphenol, epigallocatechin-3-gallate, inhibits hepatitis C virus entry

　

肝脏病学。2011年12月,54(6):1947 - 55。doi:10.1002 / hep.24610。
Ciesek S1, von Hahn T, Colpitts CC, Schang LM, Friesland M, Steinmann J, Manns MP, Ott M, Wedemeyer H, Meuleman P, Pietschmann T, Steinmann E。
作者信息
1
德国汉诺威汉诺威医学院消化内科，肝病和内分泌科。
摘要

丙型肝炎病毒(HCV)是引起肝硬化和肝细胞癌的主要原因。

目前的抗病毒治疗在相当一部分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着移植物迅速、普遍的再感染。因此，为了预防丙肝病毒感染，迫切需要针对感染早期的抗病毒策略。

在这项研究中，我们确定多酚，表没食子儿茶素-3-没食子酸酯(EGCG)，作为HCV进入的抑制剂。

绿茶儿茶素，如EGCG及其衍生物、表没食子儿茶素(EGC)、表没食子儿茶素(ECG)和表没食子儿茶素(EC)，都曾被发现具有抗病毒和抗衰老的特性。EGCG对HCV RNA复制、组装或子代病毒粒子释放均无影响。然而，它能有效抑制细胞培养来源的HCV (HCVcc)进入肝癌细胞系以及原发性人肝细胞。

这种影响与HCV基因型无关，细胞外病毒粒子感染和细胞间传播均被阻断。在HCV接种前用EGCG预处理细胞并不会减少HCV感染，而在接种过程中使用EGCG对HCV的传染性有很强的抑制作用。此外，在接种过程中直接使用EGCG对丙型肝炎病毒的传染性有很强的抑制作用。EGCG未改变所有已知HCV (co-)受体的表达水平。最后，我们发现EGCG抑制病毒附着到细胞上，从而扰乱了HCV细胞进入的初始步骤。

结论:
绿茶分子EGCG能有效抑制丙肝病毒的进入，并可能成为预防肝移植后丙肝病毒再次感染的抗病毒策略的一部分。

The green tea polyphenol, epigallocatechin-3-gallate, inhibits hepatitis C virus entry

Hepatology. 2011 Dec;54(6):1947-55. doi: 10.1002/hep.24610.
Ciesek S1, von Hahn T, Colpitts CC, Schang LM, Friesland M, Steinmann J, Manns MP, Ott M, Wedemeyer H, Meuleman P, Pietschmann T, Steinmann E.
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.

Abstract
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.

Copyright © 2011 American Association for the Study of Liver Diseases.

PMID: 21837753 DOI: 10.1002/hep.24610

https://www.ncbi.nlm.nih.gov/pubmed/21837753