Ectopic Expression of TRIM25 Restores RIG-I Expression and IFN Production Reduced by Multiple Enteroviruses 3Cpro  

作　　者：Huimin Xiao Jingliang Li Xu Yang Zhaolong Li Ying Wang Yajuan Rui Bin Liu Wenyan Zhang 

机构地区：[1]Institute of Virology and AIDS Research,Key Laboratory of Organ Regeneration and Transplantation of The Ministry of Education,The First Hospital of Jilin University,Changchun,130021,China [2]Cancer Institute(Key Laboratory of Cancer Prevention and Intervention,Ministry of Education),Second Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou,310058,China [3]Department of Hand Surgery,First Hospital of Jilin University,Changchun,130021,China [4]Changchun Institute of Biological Products Co.,Ltd,Changchun,130012,China

出　　处：《Virologica Sinica》2021年第6期1363-1374,共12页中国病毒学（英文版）

基　　金：The study was supported by the National Natural Science Foundation of China(No.81672004 and 81930062);the Science and Technology Department of Jilin Province(20190101003JH);the Key Laboratory of Molecular Virology,Jilin Province(20102209)。

摘　　要：Enteroviruses(EVs) 3C proteins suppress type I interferon(IFN) responses mediated by retinoid acid-inducible gene I(RIG-I), while an E3 ubiquitin ligase, tripartite motif protein 25(TRIM25)-mediated RIG-I ubiquitination is essential for RIG-I antiviral activity. Therefore, whether the effect of EVs 3C on RIG-I is associated with TRIM25 expression is worth to be further investigated. Here, we demonstrate that 3C proteins of EV71 and coxsackievirus B3(CVB3) reduced not only RIG-I expression but also TRIM25 expression through protease cleavage activity, while overexpression of TRIM25 restored RIG-I expression and IFN-b production reduced by 3C proteins. Further investigation confirmed that the two amino acids and functional domains in TRIM25 required for RIG-I ubiquitination and TRIM25 structural conformation were essential for the recovery of RIG-I expression. Moreover, we also observed that TRIM25 could rescue RIG-I expression reduced by 3C proteins of CVA6 and EV-D68 but not CVA16. Our findings provide an insightful interpretation of 3C-mediated host innate immune suppression and support TRIM25 as an attractive target against multiple EVs infection.

关 键 词：3C proteins RIG-I TRIM25 Innate immunity Enteroviruses(EVs) 

分 类 号：R373.2[医药卫生—病原生物学]