West nile virus ns1 antagonizes interferon beta production by targeting rig-i and mda5
文献类型：期刊论文
| 作者 | Zhang, Hong-Lei1,2; Ye, Han-Qing1; Liu, Si-Qing1; Deng, Cheng-Lin1; Li, Xiao-Dan1,2; Shi, Pei-Yong3; Zhang, Bo1 |
| 刊名 | Journal of virology
 |
| 出版日期 | 2017-09-01 |
| 卷号 | 91期号:18页码:17 |
| 关键词 | Flavivirus Ifn-beta Mda5 Ns1 Rig-i West nile virus |
| ISSN号 | 0022-538X |
| DOI | 10.1128/jvi.02396-16 |
| 通讯作者 | Zhang, bo(zhangbo@wh.iov.cn) |
| 英文摘要 | West nile virus (wnv) is a mosquito-borne flavivirus that causes epidemics of encephalitis and viscerotropic disease worldwide. this virus has spread rapidly and has posed a significant public health threat since the outbreak in new york city in 1999. the interferon (ifn)-mediated antiviral response represents an important component of virus-host interactions and plays an essential role in regulating viral replication. previous studies have suggested that multifunctional nonstructural proteins encoded by flaviviruses antagonize the host ifn response via various means in order to establish efficient viral replication. in this study, we demonstrated that the nonstructural protein 1 (ns1) of wnv antagonizes ifn-beta production, most likely through suppression of retinoic acid-inducible gene i (rig-i)-like receptor (rlr) activation. in a dual-luciferase reporter assay, wnv ns1 significantly inhibited the activation of the ifn-beta promoter after sendai virus infection or poly(i.c) treatment. ns1 also suppressed the activation of the ifn-beta promoter when it was stimulated by interferon regulatory factor 3 (irf3)/5d or its upstream molecules in the rlr signaling pathway. furthermore, ns1 blocked the phosphorylation and nuclear translocation of irf3 upon stimulation by various inducers. mechanistically, wnv ns1 targets rig-i and melanoma differentiation-associated gene 5 (mda5) by interacting with them and subsequently causing their degradation by the proteasome. furthermore, wnv ns1 inhibits the k63-linked polyubiquitination of rig-i, thereby inhibiting the activation of downstream sensors in the rlr signaling pathway. taken together, our results reveal a novel mechanism by which wnv ns1 interferes with the host antiviral response. importance wnv nile virus (wnv) has received increased attention since its introduction to the united states. however, the pathogenesis of this virus is poorly understood. this study demonstrated that the nonstructural protein 1 (ns1) of wnv antagonizes the induction of interferon beta (ifn-beta) by interacting with and degrading retinoic acid-inducible gene i (rig-i) and melanoma differentiation-associated gene 5 (mda5), which are crucial viral sensors in the host innate immune system. further experiments suggested that ns1-mediated inhibition of the rig-i-like receptor (rlr) signaling pathway involves inhibition of rig-i k63-linked polyubiquitination and that the proteasome plays a role in rig-i degradation. this study provides new insights into the regulation of wnv ns1 in the rlr signaling pathway and reveals a novel mechanism by which wnv evades the host innate immune response. the novel findings may guide us to discover new therapeutic targets and develop effective vaccines for wnv infections. |
| WOS关键词 | INDUCIBLE GENE-I ; IFN REGULATORY FACTOR-3 ; INNATE IMMUNE-RESPONSE ; INFLUENZA-A VIRUS ; DENGUE VIRUS ; SIGNALING PATHWAY ; RNA HELICASE ; NS4B PROTEIN ; IKK-EPSILON ; ACTIVATION |
| WOS研究方向 | Virology |
| WOS类目 | Virology |
| 语种 | 英语 |
| WOS记录号 | WOS:000408321600041 |
| 出版者 | AMER SOC MICROBIOLOGY |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2373373 |
| 专题 | 武汉病毒研究所 |
| 通讯作者 | Zhang, Bo |
| 作者单位 | 1.Chinese Acad Sci, Key Lab Special Pathogens & Biosafety, Ctr Emerging Infect Dis, Wuhan Inst Virol, Wuhan, Hubei, Peoples R China 2.Univ Chinese Acad Sci, Beijing, Peoples R China 3.Univ Texas Med Branch, Galveston, TX 77555 USA |
| 推荐引用方式 GB/T 7714 | Zhang, Hong-Lei,Ye, Han-Qing,Liu, Si-Qing,et al. West nile virus ns1 antagonizes interferon beta production by targeting rig-i and mda5[J]. Journal of virology,2017,91(18):17. |
| APA | Zhang, Hong-Lei.,Ye, Han-Qing.,Liu, Si-Qing.,Deng, Cheng-Lin.,Li, Xiao-Dan.,...&Zhang, Bo.(2017).West nile virus ns1 antagonizes interferon beta production by targeting rig-i and mda5.Journal of virology,91(18),17. |
| MLA | Zhang, Hong-Lei,et al."West nile virus ns1 antagonizes interferon beta production by targeting rig-i and mda5".Journal of virology 91.18(2017):17. |
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来源：武汉病毒研究所
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