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    肖宇, 吴凡, 张宝石, 等. 狂犬病病毒强、弱毒株糖蛋白调节I型干扰素作用的差异分析[J]. 华南农业大学学报, 2024, 45(2): 190-198. doi: 10.7671/j.issn.1001-411X.202211015
    引用本文: 肖宇, 吴凡, 张宝石, 等. 狂犬病病毒强、弱毒株糖蛋白调节I型干扰素作用的差异分析[J]. 华南农业大学学报, 2024, 45(2): 190-198. doi: 10.7671/j.issn.1001-411X.202211015
    shu
    XIAO Yu, WU Fan, ZHANG Baoshi, et al. The different regulatory effect of glycoproteins from virulent and attenuated strain of rabies virus on type I interferon signaling pathway[J]. Journal of South China Agricultural University, 2024, 45(2): 190-198. doi: 10.7671/j.issn.1001-411X.202211015
    Citation: XIAO Yu, WU Fan, ZHANG Baoshi, et al. The different regulatory effect of glycoproteins from virulent and attenuated strain of rabies virus on type I interferon signaling pathway[J]. Journal of South China Agricultural University, 2024, 45(2): 190-198. doi: 10.7671/j.issn.1001-411X.202211015
    shu

    狂犬病病毒强、弱毒株糖蛋白调节I型干扰素作用的差异分析

    The different regulatory effect of glycoproteins from virulent and attenuated strain of rabies virus on type I interferon signaling pathway

      摘要
    • 摘要:
      目的 狂犬病(Rabies)是由狂犬病病毒(Rabies virus，RABV)引起的一种高致死性人兽共患传染病。I型干扰素(IFN-I)通路在抵抗RABV感染中发挥重要作用。RABV可通过磷蛋白及核蛋白的功能逃逸IFN-I的抗病毒作用，本研究旨在探讨对RABV的致病性有重要影响的糖蛋白(Glycoprotein，G)在调节IFN-I通路方面扮演怎样的角色。
      方法 将RABV弱毒株Hep-Flury的G基因替换成致病株CVS-11的G基因，拯救得到重组病毒HepG，分析Hep-Flury、CVS-11和HepG这3种毒株在体内和体外感染对IFN-I通路激活和调控的差别，比较它们在神经细胞中对抗IFN-I抗病毒作用的差异性。
      结果 替换了CVS-11的G基因后，重组病毒HepG致病力增强，能够100%致死小鼠，在鼠脑中的增殖水平显著高于亲本株Hep-Flury。在感染鼠脑早期及体外神经细胞时，弱毒株Hep-Flury能够较快地激活IFN-I通路相关基因的表达，重组病毒HepG的激活能力介于Hep-Flury和CVS-11之间。利用Poly(I:C)激活神经细胞的IFN-I通路后，Hep-Flury的增殖被显著抑制，CVS-11和HepG的复制几乎不受影响，表现出一定的抵抗能力。
      结论 RABV的G蛋白在调节和抵抗IFN-I通路方面发挥重要功能，为进一步探究RABV致病毒株的G蛋白如何协助病毒在中枢神经系统中逃逸IFN-I提供了线索和依据。

       

      Abstract:
      Objective Rabies is a highly lethal zoonotic infectious disease caused by rabies virus (RABV). Type I interferon (IFN-I) pathway plays an important role in resisting RABV infection. RABV can escape the antiviral effect of IFN-I through the function of its phosphoprotein and nucleoprotein. The aim of the study was to investigate the role of glycoprotein (G), which has an important impact on the pathogenicity of RABV, in regulating IFN-I pathway needs more comprehensive exploration.
      Method This study replaced the G gene of the RABV attenuated strain Hep-Flury with the G gene of the pathogenic strain CVS-11 to rescue and acquire the recombinant virus HepG. We analyzed the differences in the activation and regulation of IFN-I pathway in vivo and in vitro infected with Hep-Flury, CVS-11 and HepG, and compared the differences of these virus strains in fighting against antiviral effect of IFN-I in nerve cells.
      Result After replacing G gene, the recombinant virus HepG had enhanced pathogenicity, was able to kill 100% of mice and the proliferation level in the mouse brain was significantly higher than that of the parental strain Hep-Flury. While infecting mouse brain early and in vitro neuronal cells, the attenuated strain Hep-Flury was able to activate the expression of IFN-I pathway-related genes faster, and the activation ability of HepG was between that of Hep-Flury and CVS-11. After activation of the IFN-I pathway in neuronal cells using Poly(I:C), the proliferation of Hep-Flury was significantly inhibited, and the replication of CVS-11 and HepG was almost unaffected, showing some resistance.
      Conclusion G protein of RABV plays an important role in regulating and resisting the IFN-I pathway, providing the clue and evidence for further exploring how the G protein of RABV pathogenic strains helps the virus escape IFN-I pathway in the central nervous system.

       

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