线粒体抗病毒信号蛋白(MAVS)在宿主天然免疫信号通路中的调节作用  

Functions and Regulation of MAVS, The Mitochondrial Antiviral Signaling Protein in Innate Immunity

作　　者：杨星星[1,2] 王凯[1] 陈晓娟[1] 邢雅玲[1] 陈忠斌[1,2] 

机构地区：[1]军事医学科学院放射与辐射医学研究所,北京100850 [2]安徽医科大学研究生院,合肥230032

出　　处：《生物化学与生物物理进展》2013年第5期397-405,共9页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金资助项目(81172799;81273231)~~

摘　　要：线粒体抗病毒信号蛋白(MAVS)作为一种接头蛋白在调节宿主天然免疫信号通路过程中扮演重要角色.Toll样受体(TLR)和RIG-Ⅰ样受体(RLR)等细胞模式识别受体识别入侵的病原体并将信号传递给MAVS,MAVS通过刺激下游的TBK1复合体和IKK复合体分别活化NF-κB和IRF3等信号通路,进而激活干扰素α/β表达,诱发细胞内抗感染天然免疫反应.MAVS除定位线粒体外,也可定位于过氧化物酶体上.MAVS在细胞内的不同定位决定了其在早期快速和持续性抗病毒天然免疫中的不同调节机制.MAVS只有同时定位在过氧化物酶体和线粒体上才可诱导干扰素刺激基因(ISG)快速且稳定地表达.本文通过对MAVS的发现、结构、细胞定位及其在天然免疫信号通路中的调控机制等最新进展进行综述,以期揭示MAVS蛋白在细胞内天然免疫信号通路中的重要调节作用,为研究病毒逃逸宿主天然免疫的机制和研究新型抗病毒免疫治疗策略提供新思路.The mitochondrial antiviral signaling adaptor, MAVS, also known as Cardif, VISA or IPS1, is critical for host defenses against viral infection by inducing expression of type-1 interferons （IFN- Ⅰ ）. The sensors of antiviral immunity, RIG- I and melanoma differentiation-associated gene 5 （MDAS）, detect the invasion pathogens, and pass the signal to MAVS, which is anchored to the mitochondrial membrane. MAVS then stimulates TBK1 and IKK complex and activates the transcription factors of IRF3/7 and NF-κB, which lead to the expression of interferon and activate antiviral innate immunity. MAVS was recently found to localize in both peroxisome and mitochondrial membrane. The peroxisomal MAVS is required for the rapid induction of antiviral effectors, whereas the mitochondrial MAVS is required for a sustained antiviral immunity response. This review focused on the discovery, domain structure and cellular localization of MAVS with an emphasis on the regulatory mechanisms of MAVS in modulating the antiviral innate immunity.

关 键 词：MAVS 天然免疫 Ⅰ型干扰素 RIG-Ⅰ TLR 

分 类 号：R392[医药卫生—免疫学] Q257[医药卫生—基础医学]