Selective estrogen receptor modulators inhibit hepatitis C virus infection at multiple steps of the virus life cycle
Selective estrogen receptor modulators inhibit hepatitis C virus infection at multiple steps of the virus life cycle
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DOI：
10.1016/j.micinf.2012.10.003
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发表时间：
2013-01-01
影响因子：
5.8
通讯作者：
Fukazawa, Hidesuke
中科院分区：
文献类型：
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作者：
Murakami, Yuko;Fukasawa, Masayoshi;Fukazawa, Hidesuke
我们使用 JFH-I 病毒培养系统筛选丙型肝炎病毒 (HCV) 抑制剂，发现选择性雌激素受体调节剂 (SERM)，如他莫昔芬、克罗米芬、雷洛昔芬和其他雌激素受体 α (ER α) 拮抗剂，可抑制 HCV 感染。前 2 小时使用 SERM 治疗以及病毒接种后 2-24 小时的治疗减少了 HCV RNA 的产生。与细胞内 HCV RNA 相比，用 SERM 处理持续感染 JFH-1 的细胞会优先抑制细胞外 HCV RNA。当我们处理两个带有HCV基因组基因型2a（JFH-1）或基因型1b的亚基因组复制子细胞时，SERM减少了HCV基因组拷贝和病毒蛋白NS5A。 SERM抑制HCV伪颗粒(HCVpp)基因型1a、1b、2a、2b和4的进入，但不抑制水泡性口炎病毒(VSV)的进入。使用 HCVpp 的进一步实验表明，他莫昔芬影响病毒与细胞的结合以及结合后事件，包括内吞作用。总的来说，SERM 似乎针对 HCV 病毒生命周期的多个步骤：附着、进入、复制和复制后事件。 SERM 可能是治疗 HCV 感染的潜在候选者。 (C) 2012 年巴斯德研究所。由 Elsevier Masson SAS 出版。版权所有。
We screened for hepatitis C virus (HCV) inhibitors using the JFH-I viral culture system and found that selective estrogen receptor modulators (SERMs), such as tamoxifen, clomifene, raloxifene, and other estrogen receptor alpha (ER alpha)antagonists, inhibited HCV infection. Treatment with SERMs for the first 2 h and treatment 2-24 h after viral inoculation reduced the production of HCV RNA. Treating persistently JFH-1 infected cells with SERMs resulted in a preferential inhibition of extracellular HCV RNA compared to intracellular HCV RNA. When we treated two subgenomic replicon cells, which harbor HCV genome genotype 2a (JFH-1) or genotype lb, SERMs reduced HCV genome copies and viral protein NS5A. SERMs inhibited the entry of HCV pseudo-particle (HCVpp) genotypes la, lb, 2a, 2b and 4 but did not inhibit vesicular stomatitis virus (VSV) entry. Further experiment using HCVpp indicated that tamoxifen affected both viral binding to cell and post-binding events including endocytosis. Taken together, SERMs seemed to target multiple steps of HCV viral life cycle: attachment, entry, replication, and post replication events. SERMs may be potential candidates for the treatment of HCV infection. (C) 2012 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.