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学科主题: 基础医学
题名:
The multi-targeted kinase inhibitor sorafenib inhibits enterovirus 71 replication by regulating IRES-dependent translation of viral proteins
作者: Gao, Meng1; Duan, Hao1; Liu, Jing1; Zhang, Hao1; Wang, Xin1; Zhu, Meng1; Guo, Jitao1; Zhao, Zhenlong1; Meng, Lirong2; Peng, Yihong1
关键词: EV71 ; Sorafenib ; IRES ; Antiviral therapy
刊名: ANTIVIRAL RESEARCH
发表日期: 2014-06-01
DOI: 10.1016/j.antiviral.2014.03.009
卷: 106, 期:6, 页:80-85
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Pharmacology & Pharmacy ; Virology
研究领域[WOS]: Pharmacology & Pharmacy ; Virology
关键词[WOS]: VIRUS GROWTH ; INITIATION ; CARCINOMA ; ICP10 ; RNA ; ACTIVATION ; INFECTION ; APOPTOSIS ; PATHWAY ; CASCADE
英文摘要:

The activation of ERR and p38 signal cascade in. host cells has been demonstrated to be essential for picornavirus enterovirus 71 (EV71) replication and up-regulation of virus-induced cyclooxygenase-2 (COX-2)/prostaglandins E-2 (PGE(2)) expression. The aim of this study was to examine the effects of sorafenib, a clinically approved anti-cancer multi-targeted kinase inhibitor, on the propagation and pathogenesis of EV71, with a view to its possible mechanism and potential use in the design of therapy regimes for Hand foot and mouth disease (HFMD) patients with life threatening neurological complications. In this study, non-toxic concentrations of sorafenib were shown to inhibit the yield of infectious progeny EV71 (clinical BC08 strain) by about 90% in three different cell types. A similar inhibitory effect of sorafenib was observed on the synthesis of both viral genomic RNA and the VP1 protein. Interestingly, sorafenib exerted obvious inhibition of the EV71 internal ribosomal entry site (IRES)-mediated translation, the first step in picornavirus replication, by linking it to a firefly luciferase reporter gene. Sorafenib was also able to prevent both EV71-induced CPE and the activation of ERR and p38, which contributes to up-regulation COX-2/PGE(2) expression induced by the virus. Overall, this study shows that sorafenib strongly inhibits EV71 replication at least in part by regulating viral IRES-dependent translation of viral proteins, indicating a novel potential strategy for the treatment of HFMD patients with severe neurological complications. To our knowledge, this is the first report that investigates the mechanism by which sorafenib inhibits EV71 replication. (C) 2014 Elsevier B.V. All rights reserved.

语种: 英语
所属项目编号: 81371816
项目资助者: National Natural Science Foundation of China (NSFC)
WOS记录号: WOS:000336827700010
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/54206
Appears in Collections:基础医学院_病原生物学系_期刊论文

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作者单位: 1.Macao Polytech Inst, Sch Hlth Sci, Macao 999078, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Dept Microbiol, Sch Basic Med Sci, Beijing 100191, Peoples R China

Recommended Citation:
Gao, Meng,Duan, Hao,Liu, Jing,et al. The multi-targeted kinase inhibitor sorafenib inhibits enterovirus 71 replication by regulating IRES-dependent translation of viral proteins[J]. ANTIVIRAL RESEARCH,2014,106(6):80-85.
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