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鉴定鸽子的抗病毒信号蛋白(MAVS)及其在抗病毒固有免疫中的作用。

Identification of pigeon mitochondrial antiviral signaling protein (MAVS) and its role in antiviral innate immunity.

机构信息

School of Agriculture and Biology, Shanghai Key Laboratory of Veterinary Biotechnology, Agriculture Ministry Key Laboratory of Urban Agriculture (South), Shanghai Jiao Tong University, 200240, Shanghai, People's Republic of China.

出版信息

Arch Virol. 2024 Jan 12;169(2):26. doi: 10.1007/s00705-023-05920-5.

DOI:10.1007/s00705-023-05920-5
PMID:38214770
Abstract

Pigeons can be infected with various RNA viruses, and their innate immune system responds to viral infection to establish an antiviral response. Mitochondrial antiviral signaling protein (MAVS), an important adaptor protein in signal transduction, plays a pivotal role in amplifying the innate immune response. In this study, we successfully cloned pigeon MAVS (piMAVS) and performed a bioinformatics analysis. The results showed that the caspase recruitment domain (CARD) and transmembrane (TM) domain are highly conserved in poultry and mammals but poorly conserved in other species. Furthermore, we observed that MAVS expression is upregulated both in pigeons and pigeon embryonic fibroblasts (PEFs) upon RNA virus infection. Overexpression of MAVS resulted in increased levels of β-interferon (IFN-β), IFN-stimulated genes (ISGs), and interleukin (ILs) mRNA and inhibited Newcastle disease virus (NDV) replication. We also found that piMAVS and human MAVS (huMAVS) induced stronger expression of IFN-β and ISGs when compared to chicken MAVS (chMAVS), and this phenomenon was also reflected in the degree of inhibition of NDV replication. Our findings demonstrate that piMAVS plays an important role in repressing viral replication by regulating the activation of the IFN signal pathway in pigeons. This study not only sheds light on the function of piMAVS in innate immunity but also contributes to a more comprehensive understanding of the innate immunity system in poultry. Our data also provide unique insights into the differences in innate immunity between poultry and mammal.

摘要

鸽子可以感染各种 RNA 病毒,其先天免疫系统会对病毒感染做出反应,从而建立抗病毒反应。线粒体抗病毒信号蛋白(MAVS)作为信号转导中的一种重要衔接蛋白,在放大先天免疫反应中起着关键作用。在本研究中,我们成功克隆了鸽子 MAVS(piMAVS)并进行了生物信息学分析。结果表明,在禽类和哺乳动物中,半胱天冬酶募集结构域(CARD)和跨膜(TM)结构域高度保守,但在其他物种中保守性较差。此外,我们观察到 RNA 病毒感染后,鸽子和鸽子胚胎成纤维细胞(PEFs)中的 MAVS 表达上调。过表达 MAVS 导致 β-干扰素(IFN-β)、干扰素刺激基因(ISGs)和白细胞介素(ILs)mRNA 的水平升高,并抑制新城疫病毒(NDV)的复制。我们还发现,与鸡 MAVS(chMAVS)相比,piMAVS 和人 MAVS(huMAVS)诱导 IFN-β 和 ISGs 的表达更强,这种现象也反映在抑制 NDV 复制的程度上。我们的研究结果表明,piMAVS 通过调节 IFN 信号通路的激活在鸽子中抑制病毒复制中发挥重要作用。本研究不仅揭示了 piMAVS 在先天免疫中的功能,也有助于更全面地了解禽类的先天免疫系统。我们的数据还提供了关于禽类和哺乳动物先天免疫之间差异的独特见解。

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本文引用的文献

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Chicken TAX1BP1 suppresses type I interferon production via degrading chicken MAVS and facilitates infectious bursal diseases virus replication.鸡 TAX1BP1 通过降解鸡 MAVS 抑制 I 型干扰素的产生,并促进传染性法氏囊病病毒的复制。
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SMART: recent updates, new developments and status in 2020.
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Nucleic Acids Res. 2021 Jan 8;49(D1):D458-D460. doi: 10.1093/nar/gkaa937.
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Bioinformatics. 2020 Apr 15;36(8):2647. doi: 10.1093/bioinformatics/btaa058.
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IRF7 Is Involved in Both STING and MAVS Mediating IFN-β Signaling in IRF3-Lacking Chickens.IRF7 参与 STING 和 MAVS 介导的 IFN-β 信号通路在缺乏 IRF3 的鸡中的作用。
J Immunol. 2019 Oct 1;203(7):1930-1942. doi: 10.4049/jimmunol.1900293. Epub 2019 Jul 31.
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Dev Comp Immunol. 2019 Apr;93:58-65. doi: 10.1016/j.dci.2018.12.006. Epub 2018 Dec 14.
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Avian infectious bronchitis virus disrupts the melanoma differentiation associated gene 5 (MDA5) signaling pathway by cleavage of the adaptor protein MAVS.禽传染性支气管炎病毒通过切割衔接蛋白线粒体抗病毒信号蛋白(MAVS)来破坏黑色素瘤分化相关基因5(MDA5)信号通路。
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Chicken TBK1 interacts with STING and is involved in IFN-β signaling regulation.鸡TBK1与STING相互作用并参与IFN-β信号调节。
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