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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, Utrecht 3584CG, The Netherlands.
概括
禽流感H5Nx病毒可以通过其血凝素 (HA) 蛋白质的突变来适应感染人类. 一个适应人类受体结合的2016年H5Nx病毒 (2.3.4.4e) 具有一个突变,与修改后的2.3.4.4b病毒HA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:
- 高致病性禽流感H5Nx病毒对鸟类和哺乳动物构成全球威胁.
- 人类对H5Nx病毒的敏感性很高,这是由于缺乏先前存在的免疫力.
- 血凝素 (HA) 蛋白质受体的结合特异性是跨物种传播的关键因素.
研究的目的:
- 调查H5Nx病毒血质素 (HA) 适应人类受体特异性的潜力.
- 为了比较不同H5Nx病毒系 (2.3.4.4e和2.3.4.4b) 对人类受体结合的适应性.
主要方法:
- 利用甘氨酸阵列来分析病毒结合.
- 进行X射线结构分析以确定蛋白质结构.
- 进行了组织和直接糖结合测试.
主要成果:
- 一个2016年H5Nx 2.3.4.4e病毒HA获得了单个Q226L突变的人类型受体结合.
- 特定的突变L133a Δ和227Q被确定为这种人类类型结合表型的关键.
- 一种经过切割修改的2016 H5Nx 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病毒系与修改后的2.3.4.4b系相比,具有更高的快速适应人类受体结合的潜力.
- 了解HA突变对于评估禽流感病毒带来的流行病风险至关重要.
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