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Journal of Integrative Agriculture
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A novel short transcript isoform of chicken IRF7 negatively regulates interferon-β production
MA Yu-chen1*, CHEN Hua-yuan1*, GAO Shen-yan1, ZHANG Xiao-zhan2, LI Yong-tao1, YANG Xia1, ZHAO Jun1, WANG Zeng1

1 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, P.R.China

2 College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou 450046, P.R.China

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I型干扰素(type I interferon, IFN-I)是保护机体抵御病原微生物感染的重要防线。干扰素调节因子(IFN regulatory factorIRF)在DNARNA病毒感染鸡后刺激机体产生IFN-I、建立抗感染免疫的过程中发挥重要作用。在哺乳动物体内,主要依赖IRF3IRF7共同调节IFN-I的表达。但是,鸡先天缺乏IRF3,主要依赖IRF7调控IFN-I的表达。目前,已在哺乳动物体内鉴定出4IRF7剪切异构体,但鸡IRF7chicken IRF7 chIRF7)是否存在类似的剪切变异及其功能均不清楚。本研究在构建chIRF7克隆过程中,鉴定出一个新的剪切异构体,命名为chIRF7-iso。序列分析发现,与chIRF7相比,chIRF7-iso包含完整的NDNA-结合结构域,但其C端存在14个差异氨基酸。随后,我们评估了chIRF7chIRF7-isoIFN-β启动子的活化能力,并以新城疫病毒弱毒疫苗株LaSota和高致病性血清4型禽腺病毒(Fowl adenovirus serotype 4, FAdV-4)作为研究对象,评估了chIRF7-iso对这两株病毒在鸡肝细胞(leghorn male hepatocellular LMH)中复制能力的影响。结果发现,chIRF7可以促进IFN-β的高水平表达,而chIRF7-isoIFN-β启动子活性及表达量无明显影响。此外,LaSotaFAdV-4在过表达chIRF7LMH细胞中复制水平较低,而在chIRF7-iso转染组细胞中增殖较好。这些结果均说明,本研究新鉴定出一种chIRF7剪切异构体,且chIRF7-iso可能通过负调控IFN-β通路而影响病毒的增殖。该研究为丰富鸡天然免疫应答奠定了基础。


 Type I interferon (IFN-I) provides an important first line to protect avian species against pathogens invasion. IFN regulatory factor 7 (IRF7) has been identified as the most important regulator for both DNA and RNA virus-induced IFN-I production in chickens. Although four splicing variants of IRF7 have been identified in mammals, it is still unclear whether alternative splicing patterns and the function of IRF7 isoform(s) exist in chickens. In this study, we reported a novel short transcript isoform of chicken IRF7 (chIRF7), termed chIRF7-iso, which contained an intact N-terminal DNA-binding domain (DBD) and 14 amino acids different from chIRF7 in the C-terminal. Overexpression of chIRF7 in chicken leghorn male hepatocellular (LMH) cells activated the IFN-β promoter and significantly inhibited Newcastle disease virus (NDV) and fowl adenovirus serotype 4 (FAdV-4) replication. Conversely, overexpression of chIRF7-iso blocked the IFN-β promoter activity and was favorable for NDV and FAdV-4 replication in vitro. Collectively, our results confirm that a novel chIRF7 isoform-mediated negative regulates IFN-β production, which will contribute to understanding the role of chIRF7 in innate antiviral response in chicken.

Keywords:  chIRF7       chIRF7 isoform              negative regulation              IFN-β  
Online: 31 December 2022  

This work was supported by grants from the National Natural Science Foundation of China (32002259) and Natural Science Foundation of Henan Province (202300410198).

Cite this article: 

MA Yu-chen, CHEN Hua-yuan, GAO Shen-yan, ZHANG Xiao-zhan, LI Yong-tao, YANG Xia, ZHAO Jun, WANG Zeng. 2022. A novel short transcript isoform of chicken IRF7 negatively regulates interferon-β production. Journal of Integrative Agriculture, Doi:10.1016/j.jia.2022.12.015

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