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Porcine epidemic diarrhea virus nsp14 inhibits NF-κB pathway activation by targeting the IKK complex and p65

查看全文 作  者:Shasha [1]Li;Fan [1]Yang;Caina [1]Ma;Weijun [1]Cao;Jinping [1]Yang;Zhenxiang [1]Zhao;Hong [1]Tian;Zixiang [1]Zhu;Haixue [1]Zheng 高影响力作者 机构地区:[1]State Key Laboratory of Veterinary Etiological Biology,National Foot and Mouth Diseases Reference Laboratory,Key Laboratory of Animal Virology of Ministry of Agriculture,Lanzhou Veterinary Research Institute,Chinese Academy of Agricultural Sciences,Lanzhou,Gansu 730046,China高影响力机构 出  处:《Animal Diseases》索引2021年第1卷第3期,共11页高影响力期刊 基  金:This work was supported by grants from the National Key R&D Program of China(2018YFD0500103 and 2017YFD0501100);the Chinese Academy of Agricultural Science and Technology Innovation Project(CAAS-ASTIP-2021-LVRI and Y2017JC55);Central Public-interest Scientific Institution Basal Research Fund(1610312016013 and 1610312017003). 摘  要:Coronaviruses(CoVs)are a group of related enveloped RNA viruses that have severe consequences in a wide variety of animals by causing respiratory,enteric or systemic diseases.Porcine epidemic diarrhea virus(PEDV)is an economically important CoV distributed worldwide that causes diarrhea in pigs.nsp14 is a nonstructural protein of PEDV that is involved in regulation of innate immunity and viral replication.However,the function and mechanism by which nsp14 modulates and manipulates host immune responses remain largely unknown.Here,we report that PEDV nsp14 is an NF-κB pathway antagonist.Overexpression PEDV nsp14 protein remarkably decreases SeV-,poly(I:C)-and TNF-α-induced NF-κB activation.Meanwhile,expression of proinflammatory cytokines is suppressed by nspl4.nsp14 inhibits the phosphorylation of IKKs by interacting with IKKs and p65.Furthermore,nsp14 suppresses TNF-α-induced phosphorylation and nuclear import of p65.Overexpression nsp14 considerably increases PEDV replication.These results suggest a novel mechanism employed by PEDV to suppress the host antiviral response,providing insights that can guide the development of antivirals against CoVs. 关 键 词:CoVs PEDV nsp14 NF-κB innate immunity
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