草鱼 cGASL 通过靶向 MITA 负调控鱼类 IFN 反应。
Grass carp cGASL negatively regulates fish IFN response by targeting MITA.
机构信息
Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China; University of Chinese Academy of Sciences, Beijing, China.
Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
出版信息
Fish Shellfish Immunol. 2019 Nov;94:871-879. doi: 10.1016/j.fsi.2019.10.010. Epub 2019 Oct 6.
Mammalian cyclic GMP-AMP synthase (cGAS) senses double-stranded (ds) DNA in the cytosol to activate the innate antiviral response. In the present study, a cGAS-like gene, namely cGASL, was cloned from grass carp Ctenopharyngodon idellus, and its role as a negative regulator of the IFN response was revealed. Phylogenetic analysis indicated that cGASL was evolutionarily closest to cGAS, but was not a true ortholog of cGAS. Overexpression of cGASL inhibited poly I:C-stimulated grass carp (gc)IFN1pro and ISRE activities. In addition, MITA-, but not TBK1-mediated activation of gcIFN1pro was impaired by cGASL. Co-immunoprecipitation and Western blot experiments indicated that cGASL interacted with MITA and TBK1, resulting in a reduction in the phosphorylation of MITA. Lastly, overexpression of cGASL reduced the transcriptional levels of several IFN-stimulated genes activated by MITA. Collectively, these data suggest that cGASL is a negative regulator of IFN response by targeting MITA in fish.
哺乳动物环鸟苷酸-腺苷酸合酶 (cGAS) 在细胞质中感知双链 (ds) DNA，从而激活先天抗病毒反应。在本研究中，从草鱼（Ctenopharyngodon idellus）中克隆了一种 cGAS 样基因，即 cGASL，并揭示了其作为 IFN 反应负调节剂的作用。系统进化分析表明，cGASL 与 cGAS 在进化上最为接近，但不是 cGAS 的真正同源物。cGASL 的过表达抑制了多聚 I:C 刺激的草鱼（gc）IFN1pro 和 ISRE 活性。此外，cGASL 抑制了 MITA-介导但不是 TBK1 介导的 gcIFN1pro 的激活。免疫共沉淀和 Western blot 实验表明，cGASL 与 MITA 和 TBK1 相互作用，导致 MITA 的磷酸化减少。最后，cGASL 的过表达降低了 MITA 激活的几种 IFN 刺激基因的转录水平。综上所述，这些数据表明 cGASL 通过靶向鱼类中的 MITA 是 IFN 反应的负调节剂。
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