title: IFN regulatory factor 10 is a negative regulator of the IFN responses in fish.
abstract: IFN regulatory factor (IRF) 10 belongs to the IRF family and exists exclusively in birds and fish. Most IRFs have been identified as critical regulators in the IFN responses in both fish and mammals; however, the role of IRF10 is unclear. In this study, we identified IRF10 in zebrafish (Danio rerio) and found that it serves as a negative regulator to balance the innate antiviral immune responses. Zebrafish IRF10 (DrIRF10) was induced by intracellular polyinosinic:polycytidylic acid in ZF4 (zebrafish embryo fibroblast-like) cells. DrIRF10 inhibited the activation of zebrafish IFN1 (DrIFN1) and DrIFN3 promoters in epithelioma papulosum cyprinid cells in the presence or absence of polyinosinic:polycytidylic acid stimulation through direct interaction with the IFN promoters, and this inhibition was also shown to block IFN signaling. Overexpression of DrIRF10 was able to abolish the induction of DrIFN1 and DrIFN3 mediated by the retinoic acid-inducible gene I-like receptors. In addition, functional domain analysis of DrIRF10 showed that either the DNA binding domain or the IRF association domain is sufficient for its inhibitory activity for IFN signaling. Lastly, overexpression of DrIRF10 decreased the transcription level of several IFN-stimulated genes, resulting in the susceptibility of host cells to spring viremia of carp virus infection. Collectively, these data suggest that DrIRF10 inhibits the expression of DrIFN1 and DrIFN3 to avoid an excessive immune response, a unique regulation mechanism of the IFN responses in lower 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.
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.
authors: Hong
authors: H
authors: Feng
authors: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
authors: Nan
authors: N
authors: Wu
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.
authors: Yi-Bing
authors: YB
authors: Zhang
authors: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
authors: Jian-Fang
authors: JF
authors: Gui
authors: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
authors: Pin
authors: P
authors: Nie
authors: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China yzhang@ihb.ac.cn.
authors: Yong-An
authors: YA
authors: Zhang
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D029941:Fish Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000502:physiology*; D007372:Interferons / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D015027:Zebrafish / Q000235:genetics / Q000276:immunology*
chemical_list: D029941:Fish Proteins; D050835:Interferon Regulatory Factors; D007372:Interferons