Skip to Content
MilliporeSigma
  • ERRα negatively regulates type I interferon induction by inhibiting TBK1-IRF3 interaction.

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

PLoS pathogens (2017-06-08)
Xiang He, Shengli Ma, Yinyin Tian, Congwen Wei, Yongjie Zhu, Feng Li, Pingping Zhang, Penghao Wang, Yanhong Zhang, Hui Zhong
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-c-Myc−Peroxidase antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anti-α-Tubulin antibody, Mouse monoclonal, clone B-5-1-2, purified from hybridoma cell culture
Sigma-Aldrich
Monoclonal Anti-HA antibody produced in mouse, clone HA-7, ascites fluid