在最近的人类H3N2血凝素中,表观症调解了受体结合模式的演变
Ruipeng Lei1, Weiwen Liang2, Wenhao O Ouyang1
1Department of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL, 61801, USA.
Nature communications
|June 18, 2024
概括
流感A病毒的血凝素受体结合部位的突变同进化,改变了其结合方式和抗原性. 这种演变影响了疫苗的兼容性,突出显示了血凝素.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 流感A病毒的血凝素 (HA) 受体结合部位 (RBS) 对于宿主细胞的进入至关重要.
- HA RBS处于不断的进化压力之下,影响病毒适应性和抗原性.
- 以前的研究表明,HA RBS与主要抗原位点之间存在重叠.
研究的目的:
- 为了研究人类H3N2流感A病毒HA RBS中特定突变 (G186D和D190N) 的共同进化.
- 阐明这些共同进化的突变的功能和抗原后果.
- 评估这些突变对流感疫苗兼容性的影响.
主要方法:
- 用X射线结晶学来确定突变的结构基础.
- 糖甘结合试验和热稳定性分析,以评估功能影响.
- 在小鼠和人类样本中进行免疫和中和实验.
- 组合性突变发生,以评估突变的组合效应.
主要成果:
- 观察到G186D和D190N突变在最近的人类H3N2群中共同演变.
- X射线结晶学显示,这些突变协调改变HA受体结合模式.
- 在G186D和D190N之间通过糖结合和热稳定性证实了表观性.
- 病毒在受体结合模式的进化与抗原性变化相关.
- 这些突变和其他突变一起影响季节性疫苗中与蛋适应突变的兼容性.
结论:
- 在塑造最近人类H3N2血凝素的演变中,表观症起着重要作用.
- HA受体结合模式表现出高度的进化性,由共同进化的突变驱动.
- 了解这些进化动态对于预测病毒行为和改进疫苗设计至关重要.
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