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However, we currently know little about the molecular events that can translate the pathogenic cues into the appropriate code for antiviral defense. Our present study reports a specific role of B cell lymphoma (Bcl)6 as a checkpoint in the initiation of the host response to cytosolic RNA viruses. Remarkably, Bcl6 specifically binds to the interferon-regulatory factor (IRF)7 loci and restrains its transcription, thereby functioning as a negative regulator for interferon (IFN)-\u03b2 production and antiviral responses. The signal-controlled turnover of the Bcl6, most likely mediated by microRNA-127, coordinates the antiviral response and inflammatory sequelae. Accordingly, de-repression of Bcl6 resulted in a phenotypic conversion of macrophages into highly potent IFN-producing cells and rendered mice more resistant to pathogenic RNA virus infection. The failure to remove the Bcl6 regulator, however, impedes the antiviral signaling and exaggerates viral pneumonia in mice. We thus reveal a novel key molecular checkpoint to orchestrate antiviral innate immunity.<\/jats:p>","DOI":"10.1038\/srep18778","type":"journal-article","created":{"date-parts":[[2016,1,5]],"date-time":"2016-01-05T10:09:16Z","timestamp":1451988556000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Bcl6 Sets a Threshold for Antiviral Signaling by Restraining IRF7 Transcriptional Program"],"prefix":"10.1038","volume":"6","author":[{"given":"Feng","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhua","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningtong","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dakang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yina","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongping","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyun","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,1,5]]},"reference":[{"key":"BFsrep18778_CR1","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1126\/science.1125676","volume":"312","author":"A Garcia-Sastre","year":"2006","unstructured":"Garcia-Sastre, A. & Biron, C. 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