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先天性免疫是机体防御病毒感染的第一道防线也是获得性免疫触发的先决条件。当病毒进入机体细胞,胞质内的感受器即被活化,而胞质感受器启动的信号最终激活STING受体,诱导产生Ⅰ型IFN和促炎性因子。2012年首次报道STING上游通路的关键分子是cGAMP,可由胞质内的cGAS催化生成,cGAMP作为人体内的第二信使,在天然免疫信号通路中发挥着重要作用。cGAMP可与接头蛋白STING结合并活化STING,进一步激活TANK结合激酶1(TBK1),诱导转录因子干扰素调节因子3(IRF3)和NF-κB入核,产生Ⅰ型IFN和细胞因子,以便机体清除入侵的病原微生物,从而防御各种病毒感染[1],维持机体健康稳态。cGAS-cGAMP-STING通路在抗病毒药物研发中的作用引起越来越多科学家的关注,本文就该通路的最新研究进展及其在抗病毒中的作用进行系统的梳理概括。
Role of cGAS-cGAMP-STING pathway in antivirus
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摘要: 先天性免疫是宿主防御病原体入侵机体的第一道防线。胞质中异常核酸的检测表明一些保守的病原相关分子模式(pathogen associated molecular patterns)引发了Ⅰ型干扰素(IFN)介导的先天性免疫反应。DNA传感器环鸟苷酸-腺苷酸合成酶(cGAS)识别并结合宿主或病原体胞质DNA,促使第二信使环鸟苷酸-腺苷酸(cGAMP)的合成并触发干扰素基因刺激蛋白(STING)依赖性下游信号传导。该文简述了cGAS-cGAMP-STING通路及其在抗病毒研究中的最新进展,为开展病毒防治研究提供新思路,为抗病毒药物的研发提供新的方向。
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关键词:
- 环鸟苷酸-腺苷酸合成酶 /
- 环鸟苷酸-腺苷酸 /
- 干扰素基因刺激蛋白 /
- 抗病毒
Abstract: Innate immunity is the host's first line defense against pathogens invading to the body. Detection of abnormal nucleic acids in the cytoplasm showed that some conserved pathogen associated molecular patterns (PAMPS) triggered type I interferon (IFN) -mediated innate immune responses. The DNA sensor— cGAS (cGAMP Synthase) recognizes and binds to host or pathogen cytoplasmic DNA, promotes the formation of the second messenger cGAMP (cyclic GMP-AMP), and triggers STING (stimulator of interferon genes) dependent downstream signaling. Here we briefly describe the latest progress of the cGAS-cGAMP-STING pathway and its important role in antivirus, and provide new ideas for virus prevention research and new direction for the development of antiviral drugs. -
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