蝙蝠流感A病毒亚型H18N11诱导纳米级的MHCII集群在宿主细胞附着上
Maria Kaukab Osman1,2,3,4, Jonathan Robert1,2,3,4, Lukas Broich5
1Institute of Virology, Medical Center-University of Freiburg, Freiburg, Germany.
Nature communications
|April 25, 2025
概括
蝙蝠流感A型病毒 (IAV) 使用一种新的蛋白质-蛋白质相互作用进入,与MHCII结合,而不是酸. 这种结合事件触发了MHCII聚类,类似于免疫突触形成.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 甲型流感病毒 (IAV) 传统上通过血凝素 (HA) 结合酸进入细胞.
- 蝙蝠IAV亚型H17N10和H18N11代表了一个独特的例外,利用主要基因相容性复合物II类 (MHCII) 作为受体.
- 蝙蝠IAVs通过蛋白质介导的病毒进入的机制在很大程度上仍未被描述.
研究的目的:
- 调查蝙蝠IAV与MHCII.II的连接的机械细节.
- 为了确定蝙蝠HA是否以多价值方式与MHCII相互作用,类似于酸结合.
- 阐明蝙蝠IAV附着对MHCII动态和聚类的影响.
主要方法:
- 使用光激活定位显微镜 (PALM) 可视化蝙蝠IAV粒子附着在固定和活细胞上的MHCII集群上.
- 一种"反向附着"方法涉及将病毒颗粒固定起来,并观察活的MHCII表达细胞.
- 单分子追踪被用来分析MHCII在对病毒颗粒的反应中的移动性和聚类.
主要成果:
- 观察到蝙蝠IAV粒子附着于先前存在的MHCII集群.
- 病毒附着导致MHCII集群的大小增加.
- 单分子追踪表明,MHCII移动性在病毒颗粒附近下降,导致局部MHCII丰富.
- 这些动态反映了在免疫突触形成期间观察到的MHCII集群.
结论:
- 蝙蝠IAV通过一种涉及多价值相互作用的机制与MHCII接触.
- 病毒对MHCII的附着会触发受体聚类,这个过程类似于免疫突触的形成.
- 这项研究揭示了一种由蛋白质-蛋白质相互作用介导的新型病毒进入模式,扩大了我们对IAV宿主热带和病原学的理解.
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