The cGas-Sting Signaling Pathway Is Required for the Innate Immune Response Against Ectromelia Virus

文献类型： 外文期刊

第一作者： Cheng, Wen-Yu

作者： Cheng, Wen-Yu;He, Xiao-Bing;Jia, Huai-Jie;Chen, Guo-Hua;Jin, Qi-Wang;Long, Zhao-Lin;Jing, Zhi-Zhong

作者机构：

关键词： innate immunity; cGas; Sting; type I interferon; ectromelia virus

期刊名称：FRONTIERS IN IMMUNOLOGY （ 影响因子：7.561； 五年影响因子：7.624 ）

ISSN： 1664-3224

年卷期： 2018 年 9 卷

页码：

收录情况： SCI

摘要： Activation of the DNA-dependent innate immune pathway plays a pivotal role in the host defense against poxvirus. Cyclic GMP-AMP synthase (cGAS) is a key cytosolic DNA sensor that produces the cyclic dinucleotide cGMP-AMP (cGAMP) upon activation, which triggers stimulator of interferon genes (STING), leading to type I Interferons (IFNs) production and an antiviral response. Ectromelia virus (ECTV) has emerged as a valuable model for investigating the host-Orthopoxvirus relationship. However, the role of cGas-Sting pathway in response to ECTV is not clearly understood. Here, we showed that murine cells (L929 and RAW264.7) mount type I IFN responses to ECTV that are dependent upon cGas, Sting, TANK binding kinase 1 (Tbk1), and interferon regulatory factor 3 (Irf3) signaling. Disruption of cGas or Sting expression in mouse macrophages blocked the type I IFN production and facilitated ECTV replication. Consistently, mice deficient in cGas or Sting exhibited lower type I IFN levels and higher viral loads, and are more susceptible to mousepox. Collectively, our study indicates that the cGas-Sting pathway is critical for sensing of ECTV infection, inducing the type I IFN production, and controlling ECTV replication.

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