Q226L突变可以将高度致病性H5 2.3.4.4e病毒转化为结合人类类型受体
María Ríos Carrasco1, Ting-Hui Lin2, Xueyong Zhu2
1Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584CG, Utrecht, The Netherlands.
bioRxiv : the preprint server for biology
|January 20, 2025
概括
高致病性禽流感H5Nx病毒可以适应人类宿主. 在2.3.4.4e病毒中发生的单一突变使得血凝素 (HA) 能够与人类受体结合,与2.3.4.4b变异不同.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 禽流感H5Nx病毒对鸟类和哺乳动物构成全球威胁.
- 人间传播很少见,但由于缺乏免疫力,可能会导致大流行.
研究的目的:
- 研究H5Nx病毒血质素 (HA) 适应人类受体特异性的潜力.
- 为了比较2.3.4.4e和2.3.4.4bH5Nx病毒HA蛋白的适应性.
主要方法:
- 使用甘氨酸阵列进行结合分析.
- 进行了X射线结构分析.
- 进行了组织和直接糖结合测试.
主要成果:
- 一个单一的Q226L突变使2016年2.3.4.4e病毒HA能够结合人类类型的受体.
- 鉴定出L133aΔ和227Q突变对于这种人型结合至关重要.
- 修改后的2.3.4.4b病毒HA显示出有限的转换到人类类型的受体特异性.
结论:
- 2.3.4.4e H5Nx病毒HA可以通过单个氨基酸替代容易适应人类受体结合.
- 特定突变 (L133aΔ,227Q) 是这种适应性转变的关键决定因素.
- 修改后的2.3.4.4b HA不太容易适应人类受体的特异性.
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