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在H5N1流感中转换宿主突变抑制血凝素抑制特定站点激活动态

Sally M Kephart¹, Kiran F Awatramani¹, Mason I Saunders¹

¹Department of Medicinal Chemistry, University of Washington, Seattle, WA, United States.

bioRxiv : the preprint server for biology

|November 24, 2025

概括

高致病性禽流感 (HPAI) H5 HA适应被使用动态学研究. 适应性突变稳定了血凝素 (HA) 并改变了融合的行为,影响了传播能力.

科学领域:

病毒学病毒学
生物化学生物化学
结构生物学结构生物学

背景情况:

人类H5N1溢出感染正在增加,引发人们对禽流感病毒适应人类传播的担忧.
血凝素 (HA) 酸稳定性和受体偏好是宿主热带性和病毒传染性的关键特征.
之前的研究从静态结构中推断出适应性突变对HA功能的影响,对H5亚型HA激活机制的理解有限.

研究的目的:

为了研究祖先和当代高度致病性禽流感 (HPAI) H5血凝素 (HA) 蛋白的激活动态.
为了确定适应性突变对HA激活机制和动态的影响.
为了探索流感HA适应的亚型特定模式.

主要方法:

利用/交换质谱法 (HDX-MS) 来分析各种H5 HA变体的激活动态.
祖先HPAI H5 HA,具有适应性突变的HA和来自人类溢出病例的当代H5 HA的比较动态.
与HA激活的结构和功能性质相关的动态测量.

主要成果:

在不同的H5 HA亚型中,已确定活性部位灵活性的变化.
证明适应性突变抑制了融合的动态,并稳定了参与HA激活的关键子单元接口.
观察到来自人类病例的当代H5 HA具有受保护的融合和适度降低的激活pH值.

结论:

流感HA激活动态揭示了与适应性突变部位相关的亚型特定模式.
在H5HA中的适应性突变影响融合的动态和子单元接口的稳定性,影响激活.
了解这些动态机制,可以了解流感HA适应和人类传播潜力的物理约束.

关键词:

这是一种H5N1流感./交换的交换方式激活方式激活方式禽流感是禽流感的一种疾病.融合蛋白质是融合蛋白质的组成部分.血凝氨酸是什么血凝氨酸流感病毒是流感的病毒.蛋白质动力学蛋白质动力学结构质谱测量结构质谱测量传输传输传输传输传输传输

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