华南农业大学学报2024,Vol.45Issue(2):190-198,9.DOI:10.7671/j.issn.1001-411X.202211015
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
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.关键词
狂犬病/狂犬病病毒/I型干扰素/糖蛋白/免疫逃逸Key words
Rabies/Rabies virus/Type Ⅰ interferon/Glycoprotein/Immune evasion分类
农业科技引用本文复制引用
肖宇,吴凡,张宝石,徐孟磊,龙家慧,罗均,郭霄峰,罗永文..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):190-198,9.基金项目
广东省基础与应用基础研究基金(2018A030313163) (2018A030313163)