自然演变的H5N1血凝素的结构决定因素,以切换其受体特异性
Kannan Tharakaraman1, Rahul Raman, Karthik Viswanathan
1Department of Biological Engineering, Koch Institute of Integrative Cancer Research, Infectious Diseases Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Cell
|June 11, 2013
概括
了解H5N1禽流感的传播是关键. 在血凝素的特定突变.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- 高致病性禽流感A型病毒 (H5N1) 的人对人传播是一个重大的公共卫生问题.
- 病毒适应人类呼吸道受体,特别是人类甘氨酸受体,是有效传播的关键因素.
研究的目的:
- 确定H5血凝素 (HA) 受体结合部位 (RBS) 的结构特征,这对于将结合偏好从禽类转换为人类甘氨酸受体是必要的.
- 确定赋予人类受体结合的突变,并评估它们对H5N1人类适应的潜力.
主要方法:
- 对H5 HA受体结合部位的结构分析.
- 致变性研究改变HA受体的结合特性.
- 对病毒与鸟类和人类甘氨酸受体的结合的评估.
主要成果:
- 为H5 HA突变建立了一个结构框架,使其能够对人类受体结合进行定量切换.
- 在较旧的H5N1菌株中,先前发现的赋予气溶传播的突变并没有诱导目前流通的H5N1菌株的定量转换.
- 来自流通的H5N1细胞群的HA可以在只需单个基对突变的情况下实现对人类受体的定量切换.
结论:
- 该研究确定了人类受体适应所需的关键H5 HA RBS特征.
- 这些发现强调,赋予人类受体结合的突变在H5N1类别之间可能有所不同.
- 鉴定到的突变可以作为潜在的标志物来监测具有大流行潜力的H5N1菌株.
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