多个LDLR家族成员作为黄热病病毒的入口受体
Zhenlu Chong1, Sean Hui2, Xueer Qiu3
1Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.
Nature
|October 30, 2025
概括
研究人员确定LRP4是黄热病病毒 (YFV) 的关键入口受体. 这一发现与LRP1和VLDLR一起,为开发对抗YFV和相关的黄状病毒提供了新的途径.
科学领域:
- 病毒学
- 细胞生物学
- 免疫学
背景情况:
- 黄热病病毒 (YFV) 是一个重要的人类病原体.
- 没有完全了解YFV的细胞进入机制.
- 识别YFV进入受体对于开发抗病毒策略至关重要.
研究的目的:
- 识别黄热病病毒 (YFV) 进入细胞的受体.
- 研究低密度脂蛋白受体 (LDLR) 家族成员在YFV感染中的作用.
- 探索YFV和相关的orthoflaviviruses的潜在治疗点.
主要方法:
- 用CRISPR-Cas9进行查以识别表面蛋白质受体.
- 候选受体的基因操纵 (切除,补充,子宫外表达).
- 在体外细胞培养感染试验.
- 使用小鼠模型和人性化小鼠模型的体内研究.
- 开发和测试可溶性诱受体 (Fc融合蛋白).
主要成果:
- 低密度脂蛋白受体4 (LRP4) 被确定为YFV入口受体.
- 通过与YFV包膜蛋白结合,LRP4调节YFV的进入.
- 在YFV抗原复合体中的相关病毒也使用LRP4.
- 确定了LRP1和非常低密度脂蛋白受体 (VLDLR) 作为额外的YFV输入受体.
- 可溶性诱受体 (LRP1- Fc,LRP4- Fc,VLDLR- Fc) 在体外和体内表现出保护作用.
- 人类肝细胞中的LRP1缺乏减少了YFV感染.
结论:
- 多个LDLR家族成员,包括LRP4,LRP1和VLDLR,作为YFV的入口受体.
- 这些受体在YFV感染和发病过程中起着重要作用.
- 已识别的受体和诱策略对开发对抗YFV和其他新出现的orthoflaviviruses有影响.
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