Volume 26, No 3, Mar 2016
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 26 Issue 3, March 2016: 288-303 | Open Access
ORIGINAL ARTICLES
The RNA-binding protein Mex3B is a coreceptor of Toll-like receptor 3 in innate antiviral response
Yan Yang1, Su-Yun Wang1, Zhe-Fu Huang1, Hong-Mei Zou1, Bing-Ru Yan2, Wei-Wei Luo2 and Yan-Yi Wang1
1Wuhan Institute of Virology, State Key Laboratory of Virology, Chinese Academy of Sciences, Hubei 430071, China
2Collaborative Innovation Center for Viral Immunology, Medical Research Institute, College of Life Sciences, Wuhan University, Hubei 430072, China
Correspondence: Yan-Yi Wang, Tel: +86-27-87198095; Fax: +86-27-87198095(wangyy@wh.iov.cn)
Recognition of viral dsRNA by Toll-like receptor 3 (TLR3) leads to induction of interferons (IFNs) and proinflammatory cytokines, and innate antiviral response. Here we identified the RNA-binding protein Mex3B as a positive regulator of TLR3-mediated signaling by expression cloning screens. Cells from Mex3b−/− mice exhibited reduced production of IFN-β in response to the dsRNA analog poly(I:C) but not infection with RNA viruses. Mex3b−/− mice injected with poly(I:C) was more resistant to poly(I:C)-induced death. Mex3B was associated with TLR3 in the endosomes. It bound to dsRNA and increased the dsRNA-binding activity of TLR3. Mex3B also promoted the proteolytic processing of TLR3, which is critical for its activation. Mutants of Mex3B lacking its RNA-binding activity inhibited TLR3-mediated IFN-β induction. These findings suggest that Mex3B acts as a coreceptor of TLR3 in innate antiviral response.
10.1038/cr.2016.16
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