中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
Japanese encephalitis virus ns5 inhibits type i interferon (ifn) production by blocking the nuclear translocation of ifn regulatory factor 3 and nf-kappa b

文献类型:期刊论文

作者Ye, Jing1,2,3,4; Chen, Zheng1,2,4; Li, Yunchuan1,2,4; Zhao, Zikai1,2,4; He, Wen1,4; Zohaib, Ali1,2,4; Song, Yunfeng1,2,4; Deng, Chenglin5; Zhang, Bo5; Chen, Huanchun1,2,4
刊名Journal of virology
出版日期2017-04-01
卷号91期号:8页码:16
ISSN号0022-538X
关键词Japanese encephalitis virus Ns5 Innate immunity Nuclear transport
DOI10.1128/jvi.00039-17
通讯作者Cao, shengbo(sbcao@mail.hzau.edu.cn)
英文摘要The type i interferon (ifn) response is part of the first-line defense against viral infection. to initiate replication, viruses have developed powerful evasion strategies to counteract host ifn responses. in the present study, we found that the japanese encephalitis virus (jev) ns5 protein could inhibit double-stranded rna (dsrna)-induced ifn-beta expression in a dose-dependent manner. our data further demonstrated that jev ns5 suppressed the activation of the ifn transcriptional factors ifn regulatory factor 3 (irf3) and nf-kappa b. however, there was no defect in the phosphorylation of irf3 and degradation of i kappa b, an upstream inhibitor of nf-kappa b, upon ns5 expression, indicating a direct inhibition of the nuclear localization of irf3 and nf-kappa b by ns5. mechanistically, ns5 was shown to interact with the nuclear transport proteins kpna2, kpna3, and kpna4, which competitively blocked the interaction of kpna3 and kpna4 with their cargo molecules, irf3 and p65, a subunit of nf-kappa b, and thus inhibited the nuclear translocation of irf3 and nf-kappa b. furthermore, overexpression of kpna3 and kpna4 restored the activity of irf3 and nf-kappa b and increased the production of ifn-kappa in ns5-expressing or jev-infected cells. additionally, an upregulated replication level of jev was shown upon kpna3 or kpna4 overexpression. these results suggest that jev ns5 inhibits the induction of type i ifn by targeting kpna3 and kpna4. importance jev is the major cause of viral encephalitis in south and southeast asia, with high mortality. however, the molecular mechanisms contributing to the severe pathogenesis are poorly understood. the ability of jev to counteract the host innate immune response is potentially one of the mechanisms responsible for jev virulence. here we demonstrate the ability of jev ns5 to interfere with the dsrna-induced nuclear translocation of irf3 and nf-kappa b by competitively inhibiting the interaction of irf3 and nf-kappa b with nuclear transport proteins. via this mechanism, jev ns5 suppresses the induction of type i ifn and the antiviral response in host cells. these findings reveal a novel strategy for jev to escape the host innate immune response and provide new insights into the pathogenesis of jev.
WOS关键词WEST-NILE-VIRUS ; INNATE ANTIVIRAL RESPONSE ; RNA POLYMERASE NS5 ; DENGUE VIRUS ; LOCALIZATION SEQUENCES ; SIGNAL-TRANSDUCTION ; RIG-I ; PROTEIN ; ACTIVATION ; ALPHA
WOS研究方向Virology
WOS类目Virology
语种英语
出版者AMER SOC MICROBIOLOGY
WOS记录号WOS:000399472200004
URI标识http://www.irgrid.ac.cn/handle/1471x/2373442
专题武汉病毒研究所
通讯作者Cao, Shengbo
作者单位1.Huazhong Agr Univ, State Key Lab Agr Microbiol, Wuhan, Hubei, Peoples R China
2.Huazhong Agr Univ, Coll Vet Med, Lab Anim Virol, Wuhan, Hubei, Peoples R China
3.Huazhong Agr Univ, Coll Life Sci & Technol, Wuhan, Hubei, Peoples R China
4.Huazhong Agr Univ, Cooperat Innovat Ctr Sustainable Pig Prod, Wuhan, Hubei, Peoples R China
5.Chinese Acad Sci, Wuhan Inst Virol, Wuhan, Hubei, Peoples R China
推荐引用方式
GB/T 7714
Ye, Jing,Chen, Zheng,Li, Yunchuan,et al. Japanese encephalitis virus ns5 inhibits type i interferon (ifn) production by blocking the nuclear translocation of ifn regulatory factor 3 and nf-kappa b[J]. Journal of virology,2017,91(8):16.
APA Ye, Jing.,Chen, Zheng.,Li, Yunchuan.,Zhao, Zikai.,He, Wen.,...&Cao, Shengbo.(2017).Japanese encephalitis virus ns5 inhibits type i interferon (ifn) production by blocking the nuclear translocation of ifn regulatory factor 3 and nf-kappa b.Journal of virology,91(8),16.
MLA Ye, Jing,et al."Japanese encephalitis virus ns5 inhibits type i interferon (ifn) production by blocking the nuclear translocation of ifn regulatory factor 3 and nf-kappa b".Journal of virology 91.8(2017):16.

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来源:武汉病毒研究所

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