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Shengjian Liang¹, Zhili Xu², Xiaoke Liu³

¹School of Basic Medical Sciences, Tsinghua University, Beijing, China. liangsj22@mails.tsinghua.edu.cn.

Nature communications

|December 6, 2025

概括

西方马类脑炎病毒 (WEEV) 已经从VLDLR转移了它的受体使用. 这项研究揭示了与WEEV相互作用的特定VLDLR域,为病毒热带和抗病毒发展提供了洞察力.

科学领域:

病毒学病毒学
结构生物学结构生物学
分子生物学分子生物学

背景情况:

西方马类脑炎病毒 (WEEV) 导致人类和马类动物的严重神经疾病.
从历史上看,WEEV利用非常低密度脂蛋白受体 (VLDLR) 进入细胞,但目前的菌株已经改变了受体热带.

研究的目的:

阐明WEEV与VLDLR互动的结构基础.
为了确定涉及WEEV绑定的特定VLDLR域.
了解WEEV受体使用转移的分子决定因素.

主要方法:

低温电子显微镜 (cryo-EM) 用于用VLDLR碎片确定WEEEV的复杂结构.
生物化学测试以评估WEEV和VLDLR相应物之间的结合亲缘关系.
针对位点的突变发生,以调查E2糖蛋白多形态在WEEV入口中的作用.

主要成果:

确定了WEEV与特定的VLDLR域 (LA1,LA2,LA3,LA5) 之间的直接相互作用.
结冷EM显示LA1和LA2在WEEV尖端蛋白的裂内结合,而LA3和LA5与E1蛋白的DIII区域相互作用.
VLDLR LA1-5 结合剂显示出对WEEV.的结合亲和力最高.
发现WEEV E2糖蛋白中的单个多态性决定了受体热带性,特定的突变增强了VLDLR介导的进入.

结论:

对WEEV-VLDLR相互作用的详细结构见解.
了解病毒葡萄糖蛋白如何调解受体结合和进入.
识别受体热带变化的关键病毒决定因素.
为开发针对WEEV和相关alphavirus的向抗病毒疗法提供了基础.

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