东方马类脑炎病毒使用VLDLR受体的结构和功能基础
Lucas J Adams1, Saravanan Raju1, Hongming Ma1,2
1Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
bioRxiv : the preprint server for biology
|November 28, 2023
概括
东部马类脑炎病毒 (EEEV) 在非常低密度脂蛋白受体 (VLDLR) 上使用多个位点进入. 设计的VLDLR诱可以中和EEEV感染并保护小鼠.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 免疫学 免疫学 免疫学
背景情况:
- 非常低密度脂蛋白受体 (VLDLR) 促进阿尔法病毒的进入,包括东部马脑炎病毒 (EEEV) 和塞米利基森林病毒 (SFV).
- VLDLR的特征是八个LDLR类型A (LA) 域,这对病毒相互作用至关重要.
研究的目的:
- 阐明EEEV与VLDLR相互作用的结构基础.
- 了解在EEEV感染中使用VLDLR域的功能影响.
- 开发一种基于VLDLR的针对EEEV的治疗策略.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于解析EEEV-VLDLR复杂结构.
- 突变和功能测试,以调查病毒结合和感染性.
- 设计和测试一个最小的VLDLR诱接收器.
主要成果:
- 通过不同的站点 (E1/E2裂和E2 A域),EEEV同时参与多个VLDLR LA域.
- 没有单一的LA域对于有效的EEEV感染至关重要或足够,这表明复杂的域利用.
- 特定的EEEV菌株通过额外的E2 B域交互点表现出改变的VLDLR结合.
- 设计的VLDLR诱受体有效中和EEEV,并在小鼠模型中提供保护.
结论:
- 对于病毒进入,EEEV采用了与VLDLR复杂的多站点交互策略.
- 针对VLDLR病毒相互作用,为EEEV提供了一个有前途的治疗途径.
- 开发的VLDLR诱受体显示出作为一种新型抗病毒治疗的潜力.
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