IR@PKUHSC  > 北京大学基础医学院  > 病原生物学系
学科主题基础医学
The multi-targeted kinase inhibitor sorafenib inhibits enterovirus 71 replication by regulating IRES-dependent translation of viral proteins
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
2014-06-01
DOI10.1016/j.antiviral.2014.03.009
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
WOS记录号WOS:000336827700010
项目编号81371816
资助机构National Natural Science Foundation of China (NSFC)
引用统计
被引频次:9[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/54206
专题北京大学基础医学院_病原生物学系
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
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GB/T 7714
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.
APA Gao, Meng.,Duan, Hao.,Liu, Jing.,Zhang, Hao.,Wang, Xin.,...&Peng, Yihong.(2014).The multi-targeted kinase inhibitor sorafenib inhibits enterovirus 71 replication by regulating IRES-dependent translation of viral proteins.ANTIVIRAL RESEARCH,106(6),80-85.
MLA Gao, Meng,et al."The multi-targeted kinase inhibitor sorafenib inhibits enterovirus 71 replication by regulating IRES-dependent translation of viral proteins".ANTIVIRAL RESEARCH 106.6(2014):80-85.
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