表儿茶素-3-没食子酸酯抑制乙肝病毒进入肝细胞

StephenW

Source: Antiviral Res  |  Posted 1 week ago
(-)-Epigallocatechin-3-gallate inhibits entry of hepatitis B virus into hepatocytes; Huang H, Tao M, Hung T, Chen J, Lin Z, Huang C; Antiviral Research (Sep 2014)


Hepatitis B virus (HBV) is a major cause of liver disease and hepatocellular carcinoma. Chronic HBV infection is currently managed with either nucleoside/nucleotide-based or interferon-based therapies, but fails to clear infection in a substantial proportion of cases, and antiviral strategies targeting the early stages of infection are therefore required for the prevention of HBV infection. In this study, we examined some common phytochemicals and identified epigallocatechin-3-gallate (EGCG) as a new inhibitor of HBV entry. EGCG, a flavonoid present in green tea extract, belongs to the subclass of catechins. We demonstrated that EGCG at a concentration of 50μM inhibited HBV entry into immortalized human primary hepatocytes by more than 80%, whereas the other four catechins tested had much weaker inhibitory effects. DMSO-differentiated HuS-E/2 cells expressed sodium taurocholate cotransporting polypeptide (NTCP), which is a receptor for HBV. Application of EGCG during HBV inoculation markedly inhibited infection in both DMSO-differentiated HuS-E/2 cells and HA-NTCP-expressing Huh7 cells. Interestingly, EGCG induced clathrin-dependent endocytosis of NTCP from the plasma membrane followed by protein degradation. In addition, EGCG inhibited the clathrin-mediated endocytosis of transferrin. Treatment of cells with EGCG had no effect on HBV genome replication or virion secretion. Moreover, the characteristic of HBV virion and the expression of known HBV entry factors were unaltered by EGCG. Finally, the antiviral activity of EGCG on HBV entry was observed using four different genotypes, A to D. These results show that the green tea-derived molecule EGCG potently inhibits HBV entry and could be used in prevention of HBV reinfection.

StephenW

资料来源：抗病毒RES|发布1个星期前
（ - ） - 表儿茶素-3-没食子酸酯抑制条目乙肝病毒进入肝细胞;黄辉，陶男，洪吨，陈静，林Z，黄℃;抗病毒研究（2014年9月）


乙型肝炎病毒（HBV）是肝脏疾病和肝细胞癌的主要病因。慢性HBV感染者目前正与任一核苷/核苷酸类或干扰素为基础的治疗管理，但不能清除感染的病例中相当大的比例，因此，需要用于预防HBV感染的靶向感染的早期阶段的抗病毒策略。在这项研究中，我们研究了一些常见的植物化学物质，并确定了儿茶素-3 - 没食子酸酯（EGCG）是乙肝病毒进入一个新的抑制剂。儿茶素，类黄酮存在于绿茶提取物，是属于儿茶素类的子类。我们表明，EGCG在50μM的浓度抑制乙肝病毒进入永生化的人原代肝细胞由80％以上，而其它四个儿茶素测试过弱得多的抑制效果。 DMSO-分化的HUS-E / 2细胞中表达牛磺胆酸钠cotransporting多肽（NTCP），它是受体的HBV。 EGCG时接种乙肝应用显着抑制感染两种DMSO分化HUS-E/2细胞和HA-NTCP表达Huh7细胞。有趣的是，EGCG诱导NTCP的网格蛋白依赖的内吞作用从质膜随后的蛋白质降解。此外，EGCG抑制转的网格蛋白介导的内吞作用。细胞的EGCG治疗对HBV基因组的复制和病毒颗粒的分泌没有影响。此外，乙肝病毒的特性，被称为乙肝病毒进入因子的表达水平不变以EGCG。最后，使用四种不同的基因型，A至D，这些结果表明，绿茶衍生分子的EGCG有效抑制HBV条目，并可能在预防HBV再感染的用于观察EGCG对HBV的条目的抗病毒活性。

王震宇

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