title: Bcl6 Sets a Threshold for Antiviral Signaling by Restraining IRF7 Transcriptional Program.
abstract: The coordination of restraining and priming of antiviral signaling constitute a fundamental aspect of immunological functions. 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)-β 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.
authors.affiliation: Department of Infectious Diseases, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Microbiology and Immunology, Key Lab of Immunology and Molecular Medicine, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 310036, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Kang
authors.affiliation: Department of Microbiology and Immunology, Key Lab of Immunology and Molecular Medicine, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 310036, China.
authors.forename: Ningtong
authors.initials: N
authors.lastname: Zhuang
authors.affiliation: Department of Microbiology and Immunology, Key Lab of Immunology and Molecular Medicine, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 310036, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Microbiology and Immunology, Key Lab of Immunology and Molecular Medicine, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 310036, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Microbiology and Immunology, Key Lab of Immunology and Molecular Medicine, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 310036, China.|MIMR-PHI Institute of Medical Research, Clayton, Victoria 3168, Australia.
authors.forename: Dakang
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Microbiology and Immunology, Key Lab of Immunology and Molecular Medicine, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 310036, China.
authors.forename: Yina
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Microbiology and Immunology, Key Lab of Immunology and Molecular Medicine, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 310036, China.
authors.forename: Hongping
authors.initials: H
authors.lastname: Yin
authors.affiliation: Department of Microbiology and Immunology, Key Lab of Immunology and Molecular Medicine, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 310036, China.|Department of Microbiology and Immunology, Nanjing University of Chinese Medicine, Nanjing 210046, China.
authors.forename: Liyun
authors.initials: L
authors.lastname: Shi
mesh_terms: D000818:Animals; D002460:Cell Line; D056970:Co-Repressor Proteins / Q000378:metabolism; D060467:Disease Resistance / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D006655:Histone Deacetylases / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D050839:Interferon Regulatory Factor-7 / Q000235:genetics* / Q000378:metabolism; D007370:Interferon Type I / Q000096:biosynthesis; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011485:Protein Binding; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000235:genetics* / Q000378:metabolism; D011956:Receptors, Cell Surface; D015398:Signal Transduction; D014158:Transcription, Genetic; D014777:Virus Diseases / Q000378:metabolism / Q000473:pathology / Q000821:virology; D000099186:Histone Deacetylase 3; D000097905:Roundabout Proteins
chemical_list: D056970:Co-Repressor Proteins; D006655:Histone Deacetylases; D050839:Interferon Regulatory Factor-7; D007370:Interferon Type I; D008565:Membrane Proteins; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D011956:Receptors, Cell Surface; D000099186:Histone Deacetylase 3; C118348:Robo3 protein, mouse; D000097905:Roundabout Proteins