狂犬病病毒利用神经皮林2作为内细胞受体,触发TGFBR1-介导的活性蛋白聚合
Ziruo Sun1, Jinqiu Wang1, Zhiyuan Wen1
1State Key Laboratory for Animal Disease Control, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
Journal of virology
|June 25, 2025
概括
狂犬病病毒 (RABV) 使用细胞膜蛋白神经素2 (NRP2) 通过启动动动因子聚合,进入细胞. 这一发现确定了NRP2作为RABV进入的新型受体,对于理解大型病原体细胞进入机制至关重要.
科学领域:
- 病毒学 病毒学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 狂犬病病毒 (RABV) 通过克拉介导的内细胞分裂 (CME) 进入细胞,但需要活性聚合才能有效地进入.
- 在RABV进入过程中启动这种actin聚合的特定受体仍然不清楚.
研究的目的:
- 为了确定细胞受体负责启动在RABV入口期间的actin聚合.
- 阐明RABV利用这种受体进入细胞的机制.
主要方法:
- 研究了细胞膜蛋白在RABV感染中的作用.
- 利用基于抗体的阻断和基因表达研究 (例如,在DU145细胞中的人类NRP2).
- 检查了蛋白质与蛋白质的相互作用 (NRP2,RABV糖蛋白,TGFBR1,Cdc42) 和F-actin的聚合.
主要成果:
- 神经素2 (NRP2) 被确定为一种新型受体,对RABV感染至关重要.
- NRP2直接与RABV糖蛋白相互作用,并启动F-actin的聚合.
- NRP2触发了TGFBR1/2-Cdc42介导的活性聚合,这种机制也被囊性口腔炎病毒使用.
结论:
- 通过启动actin聚合,NRP2充当RABV进入的新型受体.
- NRP2通过转导病毒结合信号来促进RABV细胞的进入,从而启动actin聚合.
- NRP2可能是促进大型病原体通过CME进入的关键分子.
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