鸡干扰素调节因子7剪切异构体负调控干扰素β的表达

doi:10.1016/j.jia.2022.12.015

Journal of Integrative Agriculture ›› 2023, Vol. 22 ›› Issue (7): 2213-2220.DOI: 10.1016/j.jia.2022.12.015

鸡干扰素调节因子7剪切异构体负调控干扰素β的表达

收稿日期:2022-08-18 接受日期:2022-10-17 出版日期:2023-07-20 发布日期:2022-10-17

A novel short transcript isoform of chicken IRF7 negatively regulates interferon-β production

MA Yu-chen^1*, CHEN Hua-yuan^1*, GAO Shen-yan¹, ZHANG Xiao-zhan², LI Yong-tao¹, YANG Xia¹, ZHAO Jun¹, WANG Zeng^1#

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

Received:2022-08-18 Accepted:2022-10-17 Online:2023-07-20 Published:2022-10-17
About author:MA Yu-chen, E-mail: mayc2001@126.com; #Correspondence WANG Zeng, Tel: +86-371-56990077, E-mail: wzzxz20140105@ 126.com * These authors contributed equally to this study.
Supported by:
This work was supported by the grants from the National Natural Science Foundation of China (32002259) and the Natural Science Foundation of Henan Province, China (202300410198).

摘要/Abstract

摘要： 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 factor，IRF）在DNA及RNA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IRF3和IRF7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4种IRF7剪切异构体，但鸡IRF7（chicken 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N端DNA-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chIRF7和chIRF7-iso对IFN-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-iso对IFN-β启动子活性及表达量无明显影响。此外，LaSota和FAdV-4在过表达chIRF7的LMH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。

Abstract: 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 DNAbinding 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.

Key words: chIRF7 , chIRF7 isoform , negative regulation , IFN-β

MA Yu-chen, CHEN Hua-yuan, GAO Shen-yan, ZHANG Xiao-zhan, LI Yong-tao, YANG Xia, ZHAO Jun, WANG Zeng. 鸡干扰素调节因子7剪切异构体负调控干扰素β的表达[J]. Journal of Integrative Agriculture, 2023, 22(7): 2213-2220.

MA Yu-chen, CHEN Hua-yuan, GAO Shen-yan, ZHANG Xiao-zhan, LI Yong-tao, YANG Xia, ZHAO Jun, WANG Zeng. A novel short transcript isoform of chicken IRF7 negatively regulates interferon-β production[J]. Journal of Integrative Agriculture, 2023, 22(7): 2213-2220.

参考文献

Alsamman K, El-Masry O S. 2018. Interferon regulatory factor 1 inactivation in human cancer. Bioscience Reports, 38, BSR20171672.

Au W C, Moore P A, Lafleur D W, Tombal B, Pitha P M. 1998. Characterization of the interferon regulatory factor-7 and its potential role in the transcription activation of interferon a genes. Journal of Biological Chemistry, 273, 29210-29217.

Campbell L, Magor K. 2020. Pattern recognition receptor signaling and innate responses to influenza a viruses in the mallard duck, compared to humans and chickens. Frontiers in cellular and infection microbiology, 10, 209.

Cheng Y, Zhu W, Ding C, Niu Q, Sun J. 2019. Irf7 is involved in both sting and mavs mediating ifn-β signaling in irf3-lacking chickens. Journal of Immunology, 203, 1930-1942.

Du X S, Zhou D F, Zhou J, Xue J W, Wang G H, Cheng Z Q. 2022. Marek's disease virus serine/threonine kinase us3 facilitates viral replication by targeting irf7 to block ifn-beta production. Veterinary Microbiology, 266, 109364.

Gao M, Liu Y, Wang Y, Zhang X, Dong S, Liu X. 2019. Newly identified apn splice isoforms suggest novel splicing mechanisms may underlie circrna circularization in moth. Febs Open Bio, 9, 1521-1535.

Guang-Nian, Zhao, Ding-Sheng, Jiang, Hongliang, Li. 2015. Interferon regulatory factors: At the crossroads of immunity, metabolism, and disease. Biochimica et Biophysica Acta (BBA) - Bioenergetics, 1852, 365-378.

Hayden M S, Ghosh S. 2004. Signaling to nf-kappab. Genes & Development, 18, 2195-2224.

Ivashkiv L B, Donlin L T. 2014. Regulation of type i interferon responses. Nature Reviews: Immunology, 14, 36-49.

Kenya, Honda, and, Akinori, Takaoka, and, Tadatsugu, Taniguchi. 2006. Type i interferon gene induction by the interferon regulatory factor family of transcription factors. Immunity, 25, 349-360.

Kim T H, Kern C, Zhou H. 2020. Knockout of irf7 highlights its modulator function of host response against avian influenza virus and the involvement of mapk and tor signaling pathways in chicken. Genes, 11, 385.

Lakhdari, Omar, Minev, Ivelina, McAllister, Christopher, S., Wang, Michael, Prince. 2016. Tlr3 signaling is downregulated by a mavs isoform in epithelial cells. Cellular Immunology, 310, 205-210.

Ming C, Jie Z. 2017. Alternative pre-mrna splicing in mammals and teleost fish: A effective strategy for the regulation of immune responses against pathogen infection. International Journal of Molecular Sciences, 18, 1530.

Neerukonda S N, Katneni U. 2020. Avian pattern recognition receptor sensing and signaling. Veterinary Sciences, 7, 14.

Pei-Hui W, Sin-Yee F, Wei-Wei G, Jian-Jun D, Yun C, Vidyanath C, Kit-San Y, Ting-Hin H, Ching-Ping C, Yan Z. 2018. A novel transcript isoform of sting that sequesters cgamp and dominantly inhibits innate nucleic acid sensing. Nucleic Acids Research, 46, 4054-4071.

Qin Y, Liu Q, Tian S, Xie W, Cui J, Wang R F. 2016. Trim9 short isoform preferentially promotes DNA and rna virus-induced production of type i interferon by recruiting gsk3β to tbk1. Cell Research, 26, 613-628.

Sato M, Hata N, Asagiri M, Nakaya T, Taniguchi T, Tanaka N. 1998. Positive feedback regulation of type i ifn genes by the ifn-inducible transcription factor irf-7. FEBS Letters, 441, 106-110.

Tae, Hyun, Kim, Huaijun, Zhou. 2015. Functional analysis of chicken irf7 in response to dsrna analog poly(i:C) by integrating overexpression and knockdown. PloS One, 10, e0133450.

Taniguchi T, Ogasawara K, Akinori Takaoka A, Tanaka N. 2001. Irf family of transcription factors as regulators of host defense. Annual Review of Immunology, 19, 623.

Wang Z, Ning Z, Sun M, Gao S, Kang Y, Xie P, Ren T. 2014. Interferon regulatory factor 7- (irf7-) mediated immune response affects newcastle disease virus replication in chicken embryo fibroblasts. Acta Veterinaria Hungarica, 62, 500-511.

Wei X, Qian W, Sizhu S, Li Y, Guo K, Jin M, Zhou H. 2018. Negative regulation of interferon-beta production by alternative splicing of tumor necrosis factor receptor-associated factor 3 in ducks. Frontiers in Immunology, 9, 409.

Wu W, Zhang W, Tian L, Brown B R, Metcalf J P. 2020. Irf7 is required for the second phase interferon induction during influenza virus infection in human lung epithelia. Viruses, 12, 377.

Yael, Mamane, and, Christophe, Heylbroeck, and, Pierre, Génin, and, Michele. 1999. Interferon regulatory factors: The next generation. Gene, 237, 1-14.

Yong Z, Dongsheng X, Yanjun J, Luwen Z, Masucci M G. 2010. Dual functions of interferon regulatory factors 7c in epstein-barr virus–mediated transformation of human b lymphocytes. PloS One, 5, e9459.

Zhang L, Pagano J S. 1997. Irf-7, a new interferon regulatory factor associated with epstein-barr virus latency. Molecular and Cellular Biology, 17, 5748-5757.

Zhang L, Pagano J S. 2002. Structure and function of irf-7. Journal of Interferon & Cytokine Research, 22, 95.

Zhao B, Shu C, Gao X, Sankaran B, Li P. 2016. Structural basis for concerted recruitment and activation of irf-3 by innate immune adaptor proteins. Proceedings of the National Academy of Sciences of the United States of America, 113, E3403.

鸡干扰素调节因子7剪切异构体负调控干扰素β的表达

A novel short transcript isoform of chicken IRF7 negatively regulates interferon-β production

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 0

编辑推荐

Metrics