人类感染H3N8流感A病毒受体结合适应的结构基础
Tianjiao Hao1, Yufeng Xie2,3, Yan Chai3
1Beijing Life Science Academy, Beijing, China.
Journal of virology
|February 24, 2025
概括
感染人类的禽源H3N8流感病毒表现出双受体结合,突变增强了人类受体相互作用. 由于独特的抗原部位影响疫苗疗效,进一步监测至关重要.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 公共卫生 公共卫生
背景情况:
- 禽源H3N8流感A型病毒 (IAV) 正在感染人类,引发公共卫生问题.
- IAV对新宿主的适应通常涉及血凝素 (HA) 的变化,但H3N8对人类的适应尚未完全理解.
- 以前的研究表明,人类分离的H3N8可以在之间传播,HA-G228S突变对空气传播至关重要.
研究的目的:
- 为了研究从人类分离物中获得的H3N8血凝素 (HA) 的受体结合特性.
- 阐明H3N8 HA中双受体结合的结构基础.
- 评估特定突变 (G228S,Q226L) 对H3N8 HA受体偏好和结合的影响.
主要方法:
- 对H3N8 HA蛋白序列的分析,包括对退行性编码子的识别.
- 使用鸟类和人类受体类似物对受体结合性质的研究.
- 低温电子显微镜 (Cryo-EM) 用于确定H3N8 HAs与受体类似物结合的结构.
- 突变性研究,以评估特定HA突变对受体结合的影响.
主要成果:
- H3N8 HAs 具有双重受体结合特性,主要偏爱鸟类受体.
- 替代G228S稍微增强了与人类受体的结合,而Q226L则将偏好从鸟类转移到人类受体.
- 化EM结构揭示了H3N8 HA的双受体结合能力的分子基础.
- 与H3N2相比,H3N8 HA具有不同的抗原位点,这引发了人们对当前疫苗有效性的担忧.
结论:
- 目前的H3N8人类分离体显示适应潜力,但尚未有效适应人对人传播.
- G228S突变在增强人类受体结合和病毒适应方面发挥作用.
- 独特的H3N8抗原性质需要持续监测,并可能挑战疫苗的疗效,需要持续监测和潜在的疫苗更新.
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