NOG1 downregulates type I interferon production by targeting phosphorylated interferon regulatory factor 3

文献类型： 外文期刊

第一作者： Xue, Qiao

作者： Xue, Qiao;Zhu, Zixiang;Xue, Zhaoning;Yang, Fan;Cao, Weijun;Liu, Xiangtao;Liu, Huisheng;Zheng, Haixue

作者机构：

期刊名称：PLOS PATHOGENS （ 影响因子：6.7； 五年影响因子：6.7 ）

ISSN： 1553-7366

年卷期： 2023 年 19 卷 7 期

页码：

收录情况： SCI

摘要： The innate immune system is the first line of the host's defense, and studying the mechanisms of the negative regulation of interferon (IFN) signaling is important for maintaining the balance of innate immune responses. Here, we found that the host GTP-binding protein 4 (NOG1) is a negative regulator of innate immune responses. Overexpression of NOG1 inhibited viral RNA- and DNA-mediated signaling pathways, and NOG1 deficiency promoted the antiviral innate immune response, resulting in the ability of NOG1 to promote viral replication. Vesicular stomatitis virus (VSV) and herpes simplex virus type 1 (HSV-1) infection induced a higher level of IFN-& beta; protein in NOG1 deficient mice. Meanwhile, NOG1-deficient mice were more resistant to VSV and HSV-1 infection. NOG1 inhibited type I IFN production by targeting IRF3. NOG1 was also found to interact with phosphorylated IFN regulatory factor 3 (IRF3) to impair its DNA binding activity, thereby downregulating the transcription of IFN-& beta; and downstream IFN-stimulated genes (ISGs). The GTP binding domain of NOG1 is responsible for this process. In conclusion, our study reveals an underlying mechanism of how NOG1 negatively regulates IFN-& beta; by targeting IRF3, which uncovers a novel role of NOG1 in host innate immunity. Author summaryAlthough type I IFN benefits antiviral activity, IFN aberrant secretion can trigger diseases. The study of the mechanisms of innate immune response could contribute to better disease control or vaccine design. In the present study, we, for the first time, demonstrate that the host GTP-binding protein 4 (NOG1) acts as a repressor of host innate immune responses. NOG1 negatively regulates viral RNA- and DNA-mediated signaling pathways by inhibiting the DNA binding ability of IFN regulatory factor 3 (IRF3). Our study reveals a common mechanism of NOG1 in regulating antiviral innate immunity and broadens the regulation mechanisms targeting IRF3.

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