17β-estradiol inhibits the production of infectious particles of hepatitis C virus
17β-estradiol inhibits the production of infectious particles of hepatitis C virus
复制标题
DOI：
10.1111/j.1348-0421.2010.00268.x
复制
发表时间：
2010-11-01
影响因子：
2.6
通讯作者：
Hotta, Hak
中科院分区：
文献类型：
--
作者：
Hayashida, Kazumi;Shoji, Ikuo;Hotta, Hak
丙型肝炎病毒持续感染会导致严重的肝脏疾病，如慢性肝炎、肝硬化和肝细胞癌。男性是慢性HCV感染导致肝纤维化进展的关键因素之一；因此，雌性激素可能在延缓肝纤维化进展方面发挥作用。另据报道，在感染急性期，女性比男性更有可能清除丙型肝炎病毒。这些观察结果导致作者提出一个问题：女性荷尔蒙是否能抑制 HCV 感染？在这项使用HCV J6/JFH1和Huh-7.5细胞的研究中，分析了雌性激素如17β-雌二醇（最有效的生理雌激素）和黄体酮对HCV RNA复制、HCV蛋白合成和HCV感染性颗粒（病毒粒子）产生的可能抑制作用。结果发现，E(2)而非P(4)显着抑制HCV病毒粒子的产生，但不抑制HCV RNA复制或HCV蛋白质合成。 E(2) 介导的 HCV 病毒粒子产生抑制可被核雌激素受体 (ER) 拮抗剂 ICI182780 消除。此外，使用 ER α 选择性激动剂 4, 4', 4 '-(4-丙基-[1H]-吡唑-1, 3, 5-三基)三酚 (PPT) 治疗，但不使用 ER β 选择性激动剂 2, 3-双 (4-羟苯基)-丙腈 (DPN) 或 G 蛋白偶联受体 30 (GPR30) 选择性治疗激动剂 1-(4-[6-溴苯并 1, 3 二氧杂环戊二烯-5-基]-3a, 4, 5, 9b-四氢-3H-环戊烷 [c] 喹啉-8-基)-乙酮 (G-1) 显着抑制 HCV 病毒粒子的产生。综上所述，目前的结果表明，最有效的生理雌激素 E(2) 以 ER α 依赖性方式抑制 HCV 感染颗粒的产生。
Persistent infection with hepatitis C virus causes serious liver diseases, such as chronic hepatitis, hepatic cirrhosis and hepatocellular carcinoma. The male gender is one of the critical factors in progression of hepatic fibrosis due to chronic HCV infection; thus female hormones may play a role in delaying the progression of hepatic fibrosis. It has also been reported that women are more likely than men to clear HCV in the acute phase of infection. These observations lead the present authors to the question: do female hormones inhibit HCV infection? In this study using HCV J6/JFH1 and Huh-7.5 cells, the possible inhibitory effect(s) of female hormones such as 17 beta-estradiol (the most potent physiological estrogen) and progesterone on HCV RNA replication, HCV protein synthesis and production of HCV infectious particles (virions) were analyzed. It was found that E(2), but not P(4), significantly inhibited production of the HCV virion without inhibiting HCV RNA replication or HCV protein synthesis. E(2)-mediated inhibition of HCV virion production was abolished by a nuclear estrogen receptor (ER) antagonist ICI182780. Moreover, treatment with the ER alpha-selective agonist 4, 4', 4 '- (4-propyl-[1H]-pyrazole-1, 3, 5-triyl)trisphenol (PPT), but not with the ER beta-selective agonist 2, 3-bis (4-hydroxyphenyl)-propionitrile (DPN) or the G protein-coupled receptor 30 (GPR30)-selective agonist 1-(4-[6-bromobenzo 1, 3 dioxol-5-yl]-3a, 4, 5, 9b-tetrahydro-3H-cyclopenta [c] quinolin-8-yl)-ethanone (G-1), significantly inhibited HCV virion production. Taken together, the present results suggest that the most potent physiological estrogen, E(2), inhibits the production of HCV infectious particles in an ER alpha-dependent manner.