title: Fish IRF6 is a positive regulator of IFN expression and involved in both of the MyD88 and TBK1 pathways.
abstract: Interferon (IFN) regulatory factors (IRF) are the crucial transcription factors for IFN expression, leading host cell response to viral infection. In mammals, only IRF6 is unaffected by IFN expression in the IRF family; however, in fish, a lower vertebrate, whether IRF6 is related to IFN regulation is unclear. In this study, we identified that zebrafish IRF6 was a positive regulator of IFN transcription and could be phosphorylated by both MyD88 and TBK1. First, the transcript level of cellular irf6 was upregulated by treatment with poly I:C (a mimic of viral RNAs), indicating IRF6 might be involved in the process of host cell response to viruses. Overexpression of IRF6 could upregulate IFN promoter activity significantly, meaning IRF6 is a positive regulator of IFN transcription. Subsequently, at the protein regulation level and in the interaction relationship, IRF6 was phosphorylated by and associated with both MyD88 and TBK1. In addition, overexpression of IRF6 activated the transcription of isg15, rig-i and mavs of host cells; meanwhile, the transcripts of p, m and n genes of SVCV were significantly declined in IRF6-overexpressing cells. Taken together, our data demonstrate that fish IRF6 is distinguished from the homolog of mammals by being a positive regulator of IFN transcription and phosphorylated by MyD88 and TBK1, suggesting that differences in the IRF6 regulation pattern exist between lower and higher vertebrates.
authors: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
authors: Shun
authors: S
authors: Li
authors: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors: Long-Feng
authors: LF
authors: Lu
authors: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors: Zhao-Xi
authors: ZX
authors: Wang
authors: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
authors: Dan-Dan
authors: DD
authors: Chen
authors: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China. Electronic address: yzhang@ihb.ac.cn.
authors: Yong-An
authors: YA
authors: Zhang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003530:Cyprinidae; D004847:Epithelial Cells; D050835:Interferon Regulatory Factors / Q000235:genetics* / Q000378:metabolism; D007372:Interferons / Q000235:genetics / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D011070:Poly I-C / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000276:immunology; D014779:Virus Replication; D015027:Zebrafish / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C504917:IRF6 protein, zebrafish; D050835:Interferon Regulatory Factors; C000614742:MyD88 protein, zebrafish; D053594:Myeloid Differentiation Factor 88; D029961:Zebrafish Proteins; D007372:Interferons; D017346:Protein Serine-Threonine Kinases; C000614241:TBK1L protein, zebrafish; D011070:Poly I-C
keywords: IRF6; Interferon; MyD88; Positive regulator; TBK1