title: Mint3 potentiates TLR3/4- and RIG-I-induced IFN-β expression and antiviral immune responses.
abstract: Type I IFNs (IFN-α/β) play crucial roles in the elimination of invading viruses. Multiple immune cells including macrophages recognize viral infection through a variety of pattern recognition receptors, such as Toll-like receptors (TLRs) and retinoic acid-inducible gene-I (RIG-I)-like receptors, and initiate type I IFN secretion and subsequent antiviral immune responses. However, the mechanisms by which host immune cells can produce adequate amounts of type I IFNs and then eliminate viruses effectively remain to be further elucidated. In the present study, we show that munc18-1-interacting protein 3 (Mint3) expression can be markedly induced during viral infection in macrophages. Mint3 enhances TLR3/4- and RIG-I-induced IRF3 activation and IFN-β production by promoting K63-linked polyubiquitination of TNF receptor-associated factor 3 (TRAF3). Consistently, Mint3 deficiency greatly attenuated antiviral immune responses and increased viral replication. Therefore, we have identified Mint3 as a physiological positive regulator of TLR3/4 and RIG-I-induced IFN-β production and have outlined a feedback mechanism for the control of antiviral immune responses.
authors.affiliation: Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine, Jinan, Shandong 250012, China.
authors.forename: Wanwan
authors.initials: W
authors.lastname: Huai
authors.affiliation: Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine, Jinan, Shandong 250012, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine, Jinan, Shandong 250012, China.
authors.forename: Zhongxia
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine, Jinan, Shandong 250012, China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine, Jinan, Shandong 250012, China.
authors.forename: Lihui
authors.initials: L
authors.lastname: Han
authors.affiliation: Division of Molecular Pathology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Takeharu
authors.initials: T
authors.lastname: Sakamoto
authors.affiliation: Faculty of Medicine, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Takara-machi, Kanazawa 920-8640, Japan.
authors.forename: Motoharu
authors.initials: M
authors.lastname: Seiki
authors.affiliation: Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine, Jinan, Shandong 250012, China.
authors.forename: Lining
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Qunye
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine, Jinan, Shandong 250012, China; wzhao@sdu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers; D002460:Cell Line; D000071457:DEAD Box Protein 58 / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000378:metabolism; D016899:Interferon-beta / Q000235:genetics* / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism / Q000821:virology; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D048008:TNF Receptor-Associated Factor 3 / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D054875:Ubiquitination; D014777:Virus Diseases / Q000209:etiology* / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C485530:Apba3 protein, mouse; D015415:Biomarkers; D050838:Interferon Regulatory Factor-3; D048008:TNF Receptor-Associated Factor 3; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D016899:Interferon-beta; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58
keywords: RIG-I; TLR; TRAF3; interferon; viral infection