Zebrafish FGFR3 is a negative regulator of RLR pathway to decrease IFN expression. Issue 92 (September 2019)

• Record Type: Journal Article
• Authors: Liu, Shu-Bo; Lu, Long-Feng; Lu, Xiao-Bing; Li, Shun; Zhang, Yong-An
• Is Part Of: Fish & shellfish immunology. Issue 92(2019)
• Page Start: 224
• Page End: 229
• Publication Date: 2019-09
• Subjects: FGFR3 -- Negative regulator -- Interferon -- TBK1 -- Zebrafish; CPE cytopathic effect -- EPC epithelioma papulosum cyprini (cell) -- FGF fibroblast growth factor -- FGFR fibroblast growth factor receptor -- IFN interferon -- IRF IFN regulatory factor -- ISRE IFN stimulated response element -- MAVS mitochondrial antiviral signaling protein -- MDA5 melanoma differentiation-associated gene 5 -- MITA mediator of IRF3 activation -- ORF open reading frame -- poly (I:C) polyinosinic: polycytidylic acid -- qPCR quantitative real-time PCR -- PRR pattern recognition receptor -- RIG-I retinoic acidinducible gene I -- RLR RIG-I-like receptor -- STAT the signal transducers and activators of transcription -- SVCV spring viremia of carp virus -- TBK1 TANK-binding kinase 1 -- TM transmembrane -- ZFL zebrafish liver (cell); Fishes -- Immunology -- Periodicals; Shellfish -- Immunology -- Periodicals; Poissons -- Immunologie -- Périodiques; Crustacés -- Immunologie -- Périodiques; 571.9617
• DOI: 10.1016/j.fsi.2019.06.002
• Languages: English
• ISSNs: 1050-4648

Abstract

Abstract: Fibroblast growth factor receptor (FGFR) 3 is one of the four distinct membrane-spanning tyrosine kinases required for proper skeletal development. In fish, the role of FGFR3 is still unclear. In this article, we reveal that zebrafish FGFR3 is a negative regulator of interferon (IFN) production in the innate immune response by suppressing the activity of TANK-binding kinase 1 (TBK1) in the process of virus infection. qPCR experiments demonstrate that the transcriptional level of cellular FGFR3 was upregulated by infection with spring viremia of carp virus (SVCV), indicating that FGFR3 might be involved in the process of host cell response to viral infection. Then, overexpression of FGFR3 significantly impeded the IFN promoter activity induced by a stimulator. In addition, the capabilities of a retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) system to activate IFN promoter were decreased during the overexpression of FGFR3. Subsequently, FGFR3 decreased the phosphorylation of interferon regulatory factor 3 (IRF3) and mediator of IRF3 activation (MITA) by TBK1. These findings suggest that zebrafish FGFR3 is a negative regulator of IFN by attenuating the kinase activity of TBK1, leading to the suppression of IFN expression. Highlights: The transcriptional level of zebrafish FGFR3 was upregulated by SVCV infection. Overexpression of zebrafish FGFR3 significantly impeded the IFN promoter activity. Zebrafish FGFR3 decreased the phosphorylation of IRF3 and MITA.