Constitutive overexpressed type I interferon induced downregulation of antiviral activity in medaka fish (Oryzias latipes) |
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| Affiliation: | 1. Institute of Biotechnology, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan, ROC;2. Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan, ROC;1. Department of Life Science, National Taiwan University, Taipei 10617, Taiwan;2. Institute of Molecular Medicine, National Taiwan University, Taipei 10002, Taiwan;1. School of Marine Sciences, Sun Yat-sen University, Guangzhou 510275, China;2. South China Sea Bio-Resource Exploitation and Utilization Collaborative Innovation Center, Sun Yat-sen University, Guangzhou 510275, China;3. Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, Sun Yat-sen University, Guangzhou 510275, China;1. The Fish Molecular Genetics and Biotechnology Laboratory, Aquatic Genomics Unit, School of Fisheries, Aquaculture and Aquatic Sciences, Auburn University, Auburn, AL 36849, USA;2. Department of Biology, College of Art and Sciences, Syracuse University, Syracuse, NY 13244, USA |
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| Abstract: | In fish, as well as vertebrates, type I interferons (IFNs) are important cytokines that help to provide innate, antiviral immunity. Although low amounts of IFN are constitutively secreted under normal physiological conditions, long-term and excessive IFN stimulation leads to reduced sensitivity to the IFN signal. This provides a negative feedback mechanism that prevents inappropriate responses and autoimmunity. At present, however, neither IFN desensitization nor the normal physiological role of constitutive IFN are well characterized in fish. The objective here was therefore to produce and characterize a transgenic medaka fish (Oryzias latipes), designated IFNd-Tg, that constitutively overexpressed the IFNd gene. A dual promoter expression vector was constructed for overexpression of IFNd under an EF1α promoter and a DsRed reporter gene under control of a γF-crystaline promoter. The phenotype of the IFNd-Tg fish had a lower response to poly(I:C) and increased susceptibility to nervous necrosis virus (NNV) infection compared to wild-type (WT). Furthermore, transduction of IFN signals for STAT1b, STAT2 and IRF9 were down-regulated in the IFNd-Tg fish, and expression levels of RLR signal molecules (MDA5, MITA, IRF1 and IRF3) were lower than in WT. The constitutive overexpression of IFNd resulted in desensitization of IFN-stimulation, apparently due to downregulation of IFN signal transduction, and this caused increased susceptibility to NNV. |
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| Keywords: | Type I interferon Antiviral response Transgene NNV Medaka fish |
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