ERRα negatively regulates type I interferon induction by inhibiting TBK1-IRF3 interaction

PLoS Pathogens

Yanhong Zhang¹  Congwen Wei¹  Pingping Zhang¹  Hui Zhong²  Yongjie Zhu²  Yinyin Tian²  Shengli Ma²  Penghao Wang²  Xiang He²  Feng Li² 

[1] Institute of Healthy Science, Anhui University, Hefei, Anhui, P.R. China;State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Beijing, P.R. China

关键词: 293T cells;    Vesicular stomatitis virus;    Immunoblotting;    Viral transmission;    infection;    Luciferase assay;    Luciferase;    Phosphorylation;    Protein expression;   

DOI  :  10.1371/journal.ppat.1006347

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Estrogen-related receptor α (ERRα) is a member of the nuclear receptor superfamily controlling energy homeostasis; however, its precise role in regulating antiviral innate immunity remains to be clarified. Here, we showed that ERRα deficiency conferred resistance to viral infection both in vivo and in vitro. Mechanistically, ERRα inhibited the production of type-I interferon (IFN-I) and the expression of multiple interferon-stimulated genes (ISGs). Furthermore, we found that viral infection induced TBK1-dependent ERRα stabilization, which in turn associated with TBK1 and IRF3 to impede the formation of TBK1-IRF3, IRF3 phosphorylation, IRF3 dimerization, and the DNA binding affinity of IRF3. The effect of ERRα on IFN-I production was independent of its transcriptional activity and PCG-1α. Notably, ERRα chemical inhibitor XCT790 has broad antiviral potency. This work not only identifies ERRα as a critical negative regulator of antiviral signaling, but also provides a potential target for future antiviral therapy.

【 授权许可】

CC BY