hTIM-1和信封蛋白之间的相互作用对于JEV感染很重要
Zhenjie Liang1, Junhui Pan1, Shengda Xie1
1MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.
Viruses
|July 29, 2023
概括
日本脑炎病毒 (JEV) 使用hTIM-1蛋白质通过直接与其E蛋白相互作用进入宿主细胞. 这种相互作用与酸胺结合不同,为抗JEV脑炎的抗病毒疗法提供了新的标.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 日本脑炎病毒 (JEV) 是蚊子传播的病毒性脑炎的主要原因.
- 宿主细胞进入的辅助因子,如人类TIM-1 (hTIM-1),对于JEV感染至关重要.
- 之前的研究确定了hTIM-1作为促进JEV进入的脂胺 (PS) 结合因子,但直接相互作用机制仍不清楚.
研究的目的:
- 为了阐明hTIM-1和JEV之间的直接相互作用.
- 为了确定参与hTIM-1和JEV相互作用的特定结合点.
- 探索针对hTIM-1-JEV相互作用的治疗策略.
主要方法:
- 同免疫沉降测定以确认直接相互作用.
- 位点定向的突变发生,以确定结合接口.
- 同焦显微镜用于追踪共内化和细胞内传输.
- 使用可溶性hTIM-1蛋白和hTIM-1抗体进行体外感染测定.
主要成果:
- 证明了hTIM-1与JEV E蛋白之间的直接结合.
- 确定了特定的结合部位:hTIM-1上的ND114115和JEV E蛋白上的K38.
- 在早期感染期间,显示了HTIM-1和JEV在内分体中的共同内化.
- 证实可溶性hTIM-1蛋白在体外抑制JEV感染.
- 证明hTIM-1抗体可以降低JEV感染力.
结论:
- hTIM-1通过特定的结合部位直接与JEV E蛋白相互作用,调解病毒的进入.
- 这种直接相互作用是JEV感染的关键机制,独立于以前已知的PS-TIM-1相互作用.
- 针对hTIM-1-JEV E蛋白相互作用,使用可溶性蛋白或抗体,为抗日本脑炎提供了一个有前途的治疗途径.
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