人类抗体介导的马尔堡病毒中和机制
Andrew I Flyak1, Philipp A Ilinykh2, Charles D Murin3
1Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN 37232, USA.
Cell
|February 28, 2015
概括
研究人员确定了来自马堡病毒 (MARV) 幸存者的中和抗体,这些抗体向MARV糖蛋白. 这些抗体通过与其暴露的受体结合部位结合来抑制MARV,从而提供了一种抑制菲洛病毒的新机制.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
背景情况:
- 中和抗体抑制马尔堡病毒 (MARV) 的确切机制在很大程度上是未知的.
- 了解这些机制对于开发针对菲洛病毒的有效抗病毒疗法至关重要.
研究的目的:
- 阐明对马尔堡病毒 (MARV) 中和抗体的作用机制.
- 描述MARV特异性中和抗体的结合部位和结构相互作用.
主要方法:
- 从MARV幸存者中分离和描述中和抗体.
- 结合性测试用于评估抗体与MARV和埃博拉病毒 (EBOV) 糖蛋白 (GP) 的相互作用.
- 单粒子冷电子显微镜 (cryo-EM) 用于确定抗体-GP复合物的结构.
主要成果:
- 确定了一组针对MARV糖蛋白 (GP) 的中和抗体,所有这些抗体都与一个主要的抗原位点结合.
- 几种抗体与埃博拉病毒 (EBOV) 呈现交叉反应性.
- 低温EM显示,中和抗体与MARV GP结合在受体结合部位附近,尽管有甘氨酸盖和类似粘素的域,但仍可访问该部位.
- 与MARV GP不同的是,EBOV GP的结合受到其甘氨酸盖和类域的阻碍.
结论:
- 中和MARV抗体通过结合感染性病毒的暴露受体结合部位来抑制病毒.
- 这种结合机制代表了一种新的filovirus抑制策略.
- 与EBOV GP相比,MARV GP受体结合部位的独特可访问性影响了抗体中和功效.
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