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Citation: Huimin Xiao, Jingliang Li, Xu Yang, Zhaolong Li, Ying Wang, Yajuan Rui, Bin Liu, Wenyan Zhang. Ectopic Expression of TRIM25 Restores RIG-I Expression and IFN Production Reduced by Multiple Enteroviruses 3Cpro [J].VIROLOGICA SINICA, 2021, 36(6) : 1363-1374.  http://dx.doi.org/10.1007/s12250-021-00410-x

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

  • Corresponding author: Bin Liu, kjkliubin@163.com, ORCID: http://orcid.org/0000-0001-8658-9888
    Wenyan Zhang, zhangwenyan@jlu.edu.cn, ORCID: http://orcid.org/0000-0003-4507-521X
  • Received Date: 31 January 2021
    Accepted Date: 12 April 2021
    Published Date: 25 June 2021
    Available online: 01 December 2021
  • 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-β 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.


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

      Corresponding author: Bin Liu, kjkliubin@163.com
      Corresponding author: Wenyan Zhang, zhangwenyan@jlu.edu.cn
    • 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

    Abstract: 

    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-β 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.