Induction of INKIT by Viral Infection Negatively Regulates Antiviral Responses through Inhibiting Phosphorylation of p65 and IRF3

文献类型： 外文期刊

第一作者： Lu, Bin

作者： Lu, Bin;Ren, Yujie;Sun, Xueqin;Han, Cuijuan;Wang, Hongyan;Chen, Yuxuan;Li, Wenxin;Du, Hai-Ning;Zhong, Bo;Huang, Zan;Li, Hong-Liang;Zhong, Bo;Li, Hong-Liang;Li, Hong-Liang;Peng, Qianqian;Zhu, Qiyun;Cheng, Yongbo;Cheng, Xiaoliang

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期刊名称：CELL HOST & MICROBE （ 影响因子：21.023； 五年影响因子：22.103 ）

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收录情况： SCI

摘要： The transcription factors p65 and IRF3 play key roles in the induction of cellular antiviral responses. Phosphorylation of p65 and IRF3 is required for their activity and constitutes a key checkpoint. Here we report that viral infection induced upregulation of INKIT, an inhibitor for NF-kB and IRF3 that restricted innate antiviral responses by blocking phosphorylation of p65 and IRF3. INKIT overexpression inhibited virus-induced phosphorylation of p65 and IRF3 and expression of downstream genes. In contrast, knockdown or knockout of INKIT had the opposite effect: Inkit(-/-) mice produced elevated levels of type I interferons and proinflammatory cytokines and were more resistant to lethal viral infection compared to wild-type. INKIT interacted with IKKa/b and TBK1/IKK 3, impairing the recruitment and phosphorylation of p65 and IRF3. Viral infection induced IKK-mediated phosphorylation of INKIT at Ser58, resulting in its dissociation from the IKKs. Our findings thus uncover INKIT as a regulator of innate antiviral responses.

分类号： Q1

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