{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T04:24:03Z","timestamp":1768451043172,"version":"3.49.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2020,3,5]],"date-time":"2020-03-05T00:00:00Z","timestamp":1583366400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31800728"],"award-info":[{"award-number":["31800728"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31630045"],"award-info":[{"award-number":["31630045"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31830024"],"award-info":[{"award-number":["31830024"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"State Key R&D Program of China","award":["2016YFA0502102"],"award-info":[{"award-number":["2016YFA0502102"]}]},{"name":"State Key R&D Program of China","award":["2017YFA0505800"],"award-info":[{"award-number":["2017YFA0505800"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Toll-like receptor 3 (TLR3)-mediated signaling is important for host defense against RNA virus. Upon viral RNA stimulation, toll and interleukin-1 receptor domain-containing adaptor inducing IFN-\u03b2 (TRIF) is recruited to TLR3 and then undergoes oligomerization, which is required for the recruitment of downstream molecules to transmit signals. Here, we identified zinc finger CCHC-type containing 3 (ZCCHC3) as a positive regulator of TLR3-mediated signaling. Overexpression of ZCCHC3 promoted transcription of downstream antiviral genes stimulated by the synthetic TLR3 ligand poly(I:C). ZCCHC3-deficiency markedly inhibited TLR3- but not TLR4-mediated induction of type I interferons (IFNs) and proinflammatory cytokines. Zcchc3\u2212\/\u2212 mice were more resistant to poly(I:C)- but not lipopolysaccharide-induced inflammatory death. Mechanistically, ZCCHC3 promoted recruitment of TRIF to TLR3 after poly(I:C) stimulation. Our findings reveal that ZCCHC3 plays an important role in TLR3-mediated innate immune response by promoting the recruitment of TRIF to TLR3 after ligand stimulation.<\/jats:p>","DOI":"10.1093\/jmcb\/mjaa004","type":"journal-article","created":{"date-parts":[[2020,3,2]],"date-time":"2020-03-02T12:24:43Z","timestamp":1583151883000},"page":"251-262","source":"Crossref","is-referenced-by-count":27,"title":["ZCCHC3 modulates TLR3-mediated signaling by promoting recruitment of TRIF to TLR3"],"prefix":"10.1093","volume":"12","author":[{"given":"Ru","family":"Zang","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan","family":"Lian","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuan","family":"Zhong","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong-Bing","family":"Shu","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,3,5]]},"reference":[{"key":"2020060508000733200_ref1","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1038\/35099560","article-title":"Recognition of double-stranded RNA and activation of NF-\u03baB by toll-like receptor 3","volume":"413","author":"Alexopoulou","year":"2001","journal-title":"Nature"},{"key":"2020060508000733200_ref2","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.chom.2017.01.001","article-title":"Human cytomegalovirus tegument protein UL82 inhibits STING-mediated signaling to evade antiviral immunity","volume":"21","author":"Fu","year":"2017","journal-title":"Cell Host Microbe"},{"key":"2020060508000733200_ref3","doi-asserted-by":"crossref","first-page":"6867","DOI":"10.4049\/jimmunol.179.10.6867","article-title":"Spatiotemporal mobilization of toll\/IL-1 receptor domain-containing adaptor molecule-1 in response to dsRNA","volume":"179","author":"Funami","year":"2007","journal-title":"J. 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