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Li Q, Lin L, Tong Y, et al. TRIM29 negatively controls antiviral immune response through targeting STING for degradation. Cell Discov. 2018;4:13doi: 10.1038/s41421-018-0010-9.
Li, Q., Lin, L., Tong, Y., Liu, Y., Mou, J., Wang, X., Wang, X., Gong, Y., Zhao, Y., Liu, Y., Zhong, B., Dai, L., Wei, Y. Q., Zhang, H., & Hu, H. (2018). TRIM29 negatively controls antiviral immune response through targeting STING for degradation. Cell discovery, 413. https://doi.org/10.1038/s41421-018-0010-9
Li, Qijie, et al. "TRIM29 negatively controls antiviral immune response through targeting STING for degradation." Cell discovery vol. 4 (2018): 13. doi: https://doi.org/10.1038/s41421-018-0010-9
Li Q, Lin L, Tong Y, Liu Y, Mou J, Wang X, Wang X, Gong Y, Zhao Y, Liu Y, Zhong B, Dai L, Wei YQ, Zhang H, Hu H. TRIM29 negatively controls antiviral immune response through targeting STING for degradation. Cell Discov. 2018 Mar 20;4:13. doi: 10.1038/s41421-018-0010-9. eCollection 2018. PMID: 29581886; PMCID: PMC5859251.
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Cell Discov. 2018 Mar 20;4:13. doi: 10.1038/s41421-018-0010-9. eCollection 2018.

TRIM29 negatively controls antiviral immune response through targeting STING for degradation.

Cell discovery

Qijie Li, Liangbin Lin, Yanli Tong, Yantong Liu, Jun Mou, Xiaodong Wang, Xiuxuan Wang, Yanqiu Gong, Yi Zhao, Yi Liu, Bo Zhong, Lunzhi Dai, Yu-Quan Wei, Huiyuan Zhang, Hongbo Hu

Affiliations

  1. 1Department of Rheumatology and Immunology, State Key Laboratory of Biotherapy and Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041 China.
  2. 2Department of General Practice and Lab of PTM, State Key Laboratory of Biotherapy and Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041 China.
  3. 3Cancer Center, State Key Laboratory of Biotherapy and Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041 China.
  4. 4School of Life Science, Wuhan University, Wuhan, China.

PMID: 29581886 PMCID: PMC5859251 DOI: 10.1038/s41421-018-0010-9

Abstract

Innate immune system is armed by several lines of pattern recognition receptors to sense various viral infection and to initiate antiviral immune response. This process is under a tight control and the negative feedback induced by infection and/or inflammation is critical to maintain immune homoeostasis and to prevent autoimmune disorders, however, the molecular mechanism is not fully understood. Here we report TRIM29, a ubiquitin E3 ligase, functions as an inducible negative regulator of innate immune response triggered by DNA virus and cytosolic DNA. DNA virus and cytosolic DNA stimulation induce TRIM29 expression robustly in macrophages and dendritic cells, although the basal level of TRIM29 is undetectable in those cells. TRIM29 deficiency elevates IFN-I and proinflammatory cytokine production upon viral DNA and cytosolic dsDNA stimulation. Consistently, in vivo experiments show that TRIM29-deficient mice are more resistant to HSV-1 infection than WT controls, indicated by better survival rate and reduced viral load in organs. Mechanism studies suggest that STING-TBK1-IRF3 signaling pathway in TRIM29 KO cells is significantly enhanced and the degradation of STING is impaired. Furthermore, we identify that TRIM29 targets STING for K48 ubiquitination and degradation. This study reveals TRIM29 as a crucial negative regulator in immune response to DNA virus and cytosolic DNA, preventing potential damage caused by overcommitted immune responses.

Conflict of interest statement

The authors declare that they have no conflict of interest.

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