中文摘要：

干扰素调节因子-3（interferonregulatoryfactor-3,IRF-3）是IRF家族中重要转录因子之一,在调控干扰素（interferon,IFN）基因表达和抗病毒天然免疫反应中具有重要作用.最新发现的MITA（mediator of IRF-3 activation,又称STING/ERIS）蛋白是宿主抗病毒天然免疫反应中的一种重要调节分子.病毒侵染时,MITA与IRF-3相互作用,特异性激活IRF-3,并募集TANK结合激酶1（TANKbindingkinase 1,TBK1）与IFN通路中的线粒体抗病毒信号蛋白MAVS（mitochondrial anti-viralsignaling protein）形成复合物,且MITA可被TBK1磷酸化,诱导Ⅰ型IFN及IFN刺激基因（interferonstimulate genes,ISG）的表达,诱发抗病毒天然免疫反应.同时还发现,泛素连接酶RNF5（ringfingerprotein 5）可对MITA发生泛素化修饰从而抑制其对IRF-3活化,实现对宿主抗病毒天然免疫反应负调节作用.本室研究发现,严重性急性呼吸系统综合症冠状病毒（severe acute respiratory syndromecoronavirus,SARS-CoV）和人类新型冠状病毒（human coronavirus NL63,HCoV-NL63）的木瓜样蛋白酶（papain-like protease,PLP）利用其特有的去泛素化酶（deubiquitinase,DUB）活性,通过宿主细胞泛素-蛋白酶体信号系统对IRF-3的泛素化等翻译后修饰进行调节,从而成为该种病毒逃逸机体抗病毒防御系统主要手段之一.

英文摘要：

The rapid induction of type I interferons（IFNs） at the initiation of the mammal antiviral innate immunity is strictly regulated by the activation of pre-existing transcription factors,including interferon regulatory factor 3（IRF-3）.MITA（mediator of IRF-3 activation,also called STING or ERIS） is a novel protein recently discovered as a member of the IRF-3 activation pathway.As a new regulator of IFN induction,MITA is localized at the endoplasmic reticulum（ER） and/or the mitochondrial membrane and is required for innate antiviral immune response.MITA interacts with IRF-3 and recruits the kinase TBK1（TANK binding kinase 1） to MAVS（mitochondrial anti-viral signaling protein） and RIG-I-associated complex,to allow IRF-3 phosphorylation by TBK1 and then to induce IFN expression.The ubiquitination and degradation of MITA leading to a negative regulation of antiviral innate immune response is mediated by the E3 ubiquitin ligase RNF5,which was also located at the ER and the mitochondrial membrane.We have shown that papain-like protease（PLP） of human coronavirus（CoV）（e.g.SARS-CoV or HCoV-NL63） that also acts as a coronaviral deubiquitinase（DUB） is a potent inhibitor of antiviral innate immunity by inhibiting virus-induced IRF-3 ubiquitination.This may be an important way for the virus to escape from the host innate antiviral responses.