禽传染性支气管炎病毒拮抗JAK-STAT信号通路的研究  

Infectious Bronchitis Virus Antagonizes Jak-Stat Signal Pathway

作　　者：楚红燕 宫晓倩[2] 徐丘璠 仇旭升[2] 谭磊[2] 孙英杰[2] 刘炜玮 宋翠萍[2] 钱琨 丁铲[2] 廖瑛[2] 陈丽颖 CHU Hongyan;GONG Xiaoqian;XU Qiufan;QIU Xusheng;TAN Lei;SUN Yingjie;LIU Weiwei;SONG Cuiping;QIAN Kun;DING Chan;LIAO Ying;CHEN Liying(College of Animal Medicine,Henan Agricultural University,Zhengzhou 450002,China;Shanghai Veterinary Research Institute,CAAS,Shanghai 200241,China;Jiangsu Key Laboratory of Zoonosis,Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses,Jiangsu Universities,Yangzhou University,Yangzhou 225009,China)

机构地区：[1]河南农业大学动物医学院,郑州450002 [2]中国农业科学院上海兽医研究所,上海200241 [3]扬州大学江苏高校动物重要疫病与人兽共患病防控协同创新中心,江苏省人兽共患病学重点实验室,扬州225009

出　　处：《中国动物传染病学报》2023年第4期49-56,共8页Chinese Journal of Animal Infectious Diseases

基　　金：国家重点研发项目(2017YFD0500802);国家自然科学基金(31772724);中国农业科学院上海兽医研究所中央级公益性科研院所基本科研业务费专项资金项目(2019JB03);江苏省人兽共患病学重点实验室资助项目(R2007)。

摘　　要：已有报道显示冠状病毒拮抗干扰素下游JAK-STAT信号通路,然而,关于传染性支气管炎病毒(IBV)对JAK-STAT信号通路的拮抗,鲜有报道。本文通过Western blot试验,证实IBV感染抑制STAT1和STAT2的磷酸化;间接免疫荧光实验证实IBV和nsp15核酸酶活性缺陷型重组病毒rIBV-nsp15-H238A均能抑制STAT1的核转位,说明IBV感染确实拮抗JAK-STAT信号通路,且nsp15核酸酶活性不是必需的。进一步实验证明,IBV编码的核酸内切酶nsp15,能够抑制内源性和外源性的STAT1表达,并且nsp15的核酸酶活性位点及其三聚化能力都是必需的。由于nsp15缺陷型毒株rIBV-nsp15-H238A能够跟野生型IBV一样拮抗JAK-STAT信号通路,推测IBV还编码其他蛋白,作用于JAK-STAT信号通路,需要进一步对病毒蛋白进行筛选和研究。Infectious bronchitis virus(IBV) is the fi rst coronavirus that was found in 1930.There are various IBV strains,which mainly infect chickens and cause economic loss in poultry industry.It has been reported that several coronaviruses antagonize innate immune response by inhibiting JAK-STAT signaling pathway.However,there are few reports on the antagonism of IBV to this pathway.In this study,we showed that IBV infection inhibited the phosphorylation of STAT1 and STAT2.In addition,both IBV and nsp15 ribonuclease defi cient recombinant virus rIBV-nsp15-H238A inhibited the nuclear translocation of STAT1,confi rming that IBV indeed antagonized the JAK-STAT pathway and nsp15 ribonuclease activity was not required.Further study showed that the IBV-encoded endoribonuclease nsp15 inhibited the expression of STAT1,indicating a requirement of ribonuclease activity and trimerization.

关 键 词：传染性支气管炎病毒 JAK-STAT信号通路 核糖核酸内切酶nsp15 

分 类 号：S852.65[农业科学—基础兽医学]