Cellular RNA Helicase DDX1 Is Involved in Transmissible Gastroenteritis Virus nsp14-Induced Interferon-Beta Production.
Cellular RNA Helicase DDX1 Is Involved in Transmissible Gastroenteritis Virus nsp14-Induced Interferon-Beta Production.
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细胞 RNA 解旋酶 DDX1 参与传染性胃肠炎病毒 nsp 14 诱导的干扰素 β 产生
DOI：
10.3389/fimmu.2017.00940
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发表时间：
2017
影响因子：
7.3
通讯作者：
Fang L
中科院分区：
文献类型：
--
作者：
Zhou Y;Wu W;Xie L;Wang D;Ke Q;Hou Z;Wu X;Fang Y;Chen H;Xiao S;Fang L
猪传染性胃肠炎病毒（Transmissible gastroenteritis virus，TGEV）是猪肠道致病性冠状病毒（enteropathetic coronavirus，CoV），可引起仔猪腹泻和严重脱水，给养猪业造成严重的经济损失。与大多数拮抗I型干扰素（IFN）产生的CoV不同，先前的研究表明TGEV感染在体内和体外均诱导IFN-1产生。然而，其潜在机制在很大程度上仍不清楚。在这项研究中，我们发现TGEV感染显着促进猪肾（PK-15）细胞中IFN-β的产生以及转录因子IFN调节因子3（IRF 3）和核因子-κ B（NF-κB）的激活。对TGEV编码蛋白的筛选表明，非结构蛋白14（nsp 14）是最有效的IFN-β诱导剂，并且主要通过激活NF-κB而不是IRF 3来诱导IFN-β的产生。进一步的分析表明nsp 14与DExD/H解旋酶家族成员DDX 1相互作用。特异性小干扰RNA（siRNA）敲低DDX 1可显著降低nsp 14诱导的IFN-β产生和NF-κB活化。此外，在转染DDX 1特异性siRNA的细胞中，TGEV诱导的IFN-β产生和IFN刺激基因（ISG）表达降低，表明DDX 1对TGEV诱导的IFN-β应答起重要作用。综上所述，我们的数据揭示了宿主RNA解旋酶DDX 1在TGEV诱导IFN-β应答中的潜在共激活作用，并证明nsp 14是TGEV编码蛋白中重要的IFN诱导剂。
Transmissible gastroenteritis virus (TGEV), an enteropathogenic coronavirus (CoV) of porcine, causes lethal watery diarrhea and severe dehydration in piglets and leads to severe economic losses in the swine industry. Unlike most CoVs that antagonize type I interferon (IFN) production, previous studies showed that TGEV infection induces IFN-I production both in vivo and in vitro. However, the underlying mechanism(s) remain largely unknown. In this study, we found that TGEV infection significantly facilitated IFN-β production as well as activation of the transcription factors IFN regulatory factor 3 (IRF3) and nuclear factor-kappaB (NF-κB) in porcine kidney (PK-15) cells. Screening of TGEV-encoded proteins demonstrated that non-structural protein 14 (nsp14) was the most potent IFN-β inducer and induced IFN-β production mainly by activating NF-κB but not IRF3. Further analysis showed that nsp14 interacted with DDX1, a member of the DExD/H helicase family. Knockdown of DDX1 by specific small interfering RNA (siRNA) significantly decreased nsp14-induced IFN-β production and NF-κB activation. Furthermore, TGEV-induced IFN-β production and IFN-stimulated gene (ISG) expression were decreased in cells transfected with DDX1-specific siRNA, indicating the vital role of DDX1 to TGEV-induced IFN-β responses. In summary, our data revealed a potential coactivator role of host RNA helicase DDX1 to the induction of IFN-β response initiated by TGEV and demonstrated that nsp14 is an important IFN inducer among the TGEV-encoded proteins.
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DOI：
10.1038/nrmicro.2016.81
发表时间：
2016-08
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
de Wit E;van Doremalen N;Falzarano D;Munster VJ
通讯作者：
Munster VJ
影响因子：
5.4
作者：
Cruz, Jazmina L. G.;Becares, Martina;Zuniga, Sonia
通讯作者：
Zuniga, Sonia
影响因子：
4.4
作者：
Errington, Fiona;Steele, Lynette;Melcher, Alan
通讯作者：
Melcher, Alan
影响因子：
12.7
作者：
Fang, Xiaonan;Gao, Jinrong;Ye, Linbai
通讯作者：
Ye, Linbai
影响因子：
5.4
作者：
Hu, Yong;Li, Wei;Cao, Cheng
通讯作者：
Cao, Cheng