title: MSX1 Modulates RLR-Mediated Innate Antiviral Signaling by Facilitating Assembly of TBK1-Associated Complexes.
abstract: Recognition of viral dsRNA by the retinoic acid-inducible gene-1-like receptors (RLRs) triggers signaling cascades that lead to activation of the TBK1 kinase and transcription factor IFN regulatory factor 3, induction of downstream antiviral genes, and innate antiviral responses. In this study, we identified muscle segment homeobox1 (MSX1) as an important modulator of RLR-mediated signaling pathways. Knockdown or knockout of MSX1 significantly impaired Sendai virus-triggered activation of TBK1 and IFN regulatory factor 3, induction of downstream antiviral genes, and cellular antiviral responses. Interestingly, MSX1 was translocated from the nucleus to cytoplasm, particularly mitochondria upon infection of Sendai virus. Biochemcially, MSX1 was important for assembly of TBK1/IKK-related kinase-associated protein 1/TNFR-associated factor-associated NF-κB activator complexes. Our results suggest that MSX1 is an important component of RLR-mediated signaling and reveal mechanisms on innate immune responses against RNA viruses.
authors.affiliation: College of Life Sciences, Medical Research Institute, Collaborative Innovation Center for Viral Immunology, Wuhan University, Wuhan 430072, China.
authors.forename: Liu-Ting
authors.identifier: 0000-0001-9962-5286
authors.initials: LT
authors.lastname: Chen
authors.affiliation: College of Life Sciences, Medical Research Institute, Collaborative Innovation Center for Viral Immunology, Wuhan University, Wuhan 430072, China.
authors.forename: Ming-Ming
authors.identifier: 0000-0001-9667-7662
authors.initials: MM
authors.lastname: Hu
authors.affiliation: College of Life Sciences, Medical Research Institute, Collaborative Innovation Center for Viral Immunology, Wuhan University, Wuhan 430072, China.
authors.forename: Zhi-Sheng
authors.identifier: 0000-0001-7034-0666
authors.initials: ZS
authors.lastname: Xu
authors.affiliation: College of Life Sciences, Medical Research Institute, Collaborative Innovation Center for Viral Immunology, Wuhan University, Wuhan 430072, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Life Sciences, Medical Research Institute, Collaborative Innovation Center for Viral Immunology, Wuhan University, Wuhan 430072, China shuh@whu.edu.cn.
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Shu
mesh_terms: D002478:Cells, Cultured; D000071457:DEAD Box Protein 58 / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000378:metabolism; D051957:MSX1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology* / Q000821:virology; D008928:Mitochondria / Q000378:metabolism*; D055503:Protein Multimerization; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport; D012367:RNA, Viral / Q000276:immunology; D011971:Receptors, Immunologic; D010253:Respirovirus Infections / Q000276:immunology*; D029082:Sendai virus / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D050838:Interferon Regulatory Factor-3; D051957:MSX1 Transcription Factor; C484083:MSX1 protein, human; D012367:RNA, Viral; D011971:Receptors, Immunologic; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58