Zhou Yu, Li Feng-Yang, Lu Long-Feng, Hu Ya-Zhen, Zhang Yong-An
State Key Laboratory of Agricultural Microbiology, College of Fisheries, Huazhong Agricultural University, Wuhan, China.
Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
Dev Comp Immunol. 2022 Jul;132:104402. doi: 10.1016/j.dci.2022.104402. Epub 2022 Mar 26.
Mammalian cyclic GMP-AMP synthase (cGAS) is pivotal for cytosolic DNA-triggered interferon (IFN) response. However, the function of cGAS in fish IFN response remains unclear. Our recent study has reported that cGAS from crucian and grass carps downregulates the IFN response by attenuating the K63-linked ubiquitination of retinoic acid-inducible gene-I (RIG-I) and its interaction with mitochondrial antiviral signaling protein (MAVS). Here, the function of crucian carp cGAS was further investigated. We found that crucian carp cGAS directly binds to poly deoxyadenylic-deoxythymidylic acid (poly (dA:dT)) and exhibits mediator of IFN regulatory factor 3 (IRF3) activation (MITA)-dependent activation of the IFN response, indicating a conserved function of crucian carp cGAS in the MITA-mediated IFN signaling. However, crucian carp cGAS could suppress the IFN activation stimulated by polyinosinic: polycytidylic acid (poly (I:C)) in time- and dose-dependent manners. These data collectively suggest complicated functions of crucian carp cGAS in the IFN antiviral response.
哺乳动物的环鸟苷酸-腺苷酸合成酶（cGAS）对于胞质DNA触发的干扰素（IFN）反应至关重要。然而，cGAS在鱼类IFN反应中的功能仍不清楚。我们最近的研究报道，鲫鱼和草鱼的cGAS通过减弱视黄酸诱导基因I（RIG-I）的K63连接的泛素化及其与线粒体抗病毒信号蛋白（MAVS）的相互作用来下调IFN反应。在此，进一步研究了鲫鱼cGAS的功能。我们发现鲫鱼cGAS直接结合聚脱氧腺苷酸-脱氧胸苷酸（poly (dA:dT)），并表现出依赖干扰素调节因子3（IRF3）激活介质（MITA）的IFN反应激活，表明鲫鱼cGAS在MITA介导的IFN信号传导中具有保守功能。然而，鲫鱼cGAS可以时间和剂量依赖性方式抑制聚肌苷酸:聚胞苷酸（poly (I:C)）刺激的IFN激活。这些数据共同表明鲫鱼cGAS在IFN抗病毒反应中具有复杂的功能。
