鼠肝表达不变是一种进化保存的抗病毒效应剂,限制人类和小鼠肝炎病毒
Yudi Zhang1, Volker Kinast2,3, Julie Sheldon1
1Institute for Experimental Virology, TWINCORE Centre for Experimental and Clinical Infection Research, Hannover, Germany.
Microbiology spectrum
|June 21, 2023
概括
鼠标无转移 (mSHFL) 蛋白质限制了C型肝炎病毒 (HCV) 和动物肝炎病毒 (RHV) 的复制. 这种古老的抗病毒效应器针对病毒RNA,为开发HCV动物模型和疫苗提供了洞察力.
科学领域:
- 病毒学和免疫学 病毒学和免疫学
- 宿主-病原体相互作用
- 天生的抗病毒免疫力.
背景情况:
- 小鼠对人类C型肝炎病毒 (HCV) 感染有抗性,限制了动物模型的开发.
- 已知干扰素 (IFN) 调节基因 (IRG) 在人类细胞中限制HCV.
- 动物肝炎病毒 (RHV) 在野生动物中循环,这表明保存了宿主-病原体动态.
研究的目的:
- 为了调查肝脏内在宿主因素是否广泛限制与远距离相关的肝炎病毒.
- 确定IFN调节基因Shiftless (Shfl) 在限制HCV和RHV中的作用.
- 探索mSHFL在了解HCV跨物种传播和开发动物模型方面的潜力.
主要方法:
- 在人类和动物肝瘤细胞系中,小鼠SHFL (mSHFL) 的子宫外表达.
- 在小鼠肝脏瘤细胞内源性mShfl的基因编辑.
- 混焦显微镜用于评估mSHFL与病毒RNA中间体的同位化.
- 对SHFL指域的突变分析.
主要成果:
- 宫外mSHFL抑制了HCV和RHV复制体的复制.
- 内源性mShfl的基因编辑增加了HCV复制和病毒产生.
- mSHFL与病毒dSRNA中间体结合,其指域的破坏取消了抗病毒活性.
结论:
- SHFL是一种古老的抗病毒效应剂,在人类和动物中具有保留的功能.
- mSHFL通过向病毒RNA来限制远距离相关的肝炎病毒 (包括HCV) 的复制.
- 这些发现突出了mSHFL在限制小鼠感染HCV的作用,并为开发关键的HCV动物模型提供了信息.
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