受体结合的H5禽流感病毒是可以通过小传播的受体
Xiaoli Xiong1, Peter J Coombs, Stephen R Martin
1MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
Nature
|April 26, 2013
概括
流感病毒的传染性是由细胞表面受体结合决定的. 一种可传播的H5N1突变体表现出增加的人类受体亲和力和独特的结合方式,促进人与人之间的传播.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 生物物理学的生物物理.
背景情况:
- 流感病毒的细胞表面受体结合决定了物种之间和人类内部的传染性.
- 高致病性禽类H5N1病毒对公众健康构成威胁,并且可以适应人类的受体.
- 传染性实验发现了一种突变的H5N1病毒,能够在中传播,这是人类流感的模型.
研究的目的:
- 量化测量可传播的H5N1突变血素 (HA) 的受体结合特性.
- 了解改变受体结合和传播能力的结构基础.
- 开发基于HA受体相互作用的病毒狂热的预测算法.
主要方法:
- 对HA受体结合亲和力的定量生物物理测量.
- 对病毒和HA结合数据的分析,以导出预测算法.
- 结晶结构测定可传播突变HA与受体类似物复合的结晶结构.
主要成果:
- 可传播的突变HA在人类受体亲和度略有增加,在鸟类受体亲和度显著下降.
- 一个衍生算法预测突变病毒对人类而不是鸟类受体的偏好是200倍.
- 晶体结构显示了类似于流行性流感菌株的人类受体结合形状,与野生型H5N1.1不同.
结论:
- 在HA中发生的Gln226Leu替代是导致受体偏好从鸟类转变为人类的原因.
- 改变的结合方式和偏好是导致突变病毒获得传染性的关键因素.
- 了解这些分子机制对于预测和控制流感大流行潜力至关重要.
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