在H5N1流感病毒中,宿主切换突变会抑制血凝素,抑制特定位点的激活动态
Sally M Kephart1, Kiran F Awatramani1, Mason I Saunders1
1Department of Medicinal Chemistry, University of Washington, Seattle, WA, USA.
Nature communications
|December 5, 2025
概括
高致病性禽流感 (HPAI) 病毒适应人类传播是令人担忧的. 在H5血凝素 (HA) 中的适应性突变稳定了它的结构,抑制了动态,并可能增加了可传播性.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 生物物理学的生物物理.
背景情况:
- 高致病性禽流感 (HPAI) H5N1的人类感染正在增加,这引发了人们对潜在的人与人传染的担忧.
- 血凝素 (HA) 酸稳定性和受体结合是影响禽流感病毒宿主热带性和传染性的关键因素.
- 之前的研究从静态结构中推断出HA的功能,使H5亚型HA的激活机制不明朗.
研究的目的:
- 调查祖先,适应和当代H5 HPAI血质素 (HA) 的激活动态.
- 阐明适应性突变对HA功能和激活机制的影响.
- 将H5 HA激活动态与H1和H3 HA激活动态进行比较.
主要方法:
- 利用/交换质谱法 (HDX-MS) 来分析各种H5 HPAI HA变体的激活动态.
- 检查了受体结合部位的灵活性和融合的动态.
- 评估了参与HA激活的关键接口的稳定性.
主要成果:
- 在不同H5HA亚型中鉴定了受体结合位灵活性的变化.
- 证明了适应性突变抑制了融合的动态,稳定了关键激活接口.
- 观察到来自溢出事件的当代H5 HA具有受保护的融合和与祖先HA相比适度低的激活pH值.
结论:
- H5 HPAI HA中的适应性突变通过稳定蛋白质结构和改变融合的行为来影响激活动态.
- 这些发现提供了对控制流感HA适应增加传播能力的物理约束和亚型特定模式的见解.
- 了解这些动态对于评估禽流感病毒的流行病潜力至关重要.
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