进化保存的氨基酸在MHC-II中介于蝙蝠流感A病毒进入人类细胞
Okikiola M Olajide1,2,3,4, Maria Kaukab Osman1,2,3,4, Jonathan Robert1,2,3,4
1Institute of Virology, Medical Center - University of Freiburg, Freiburg, Germany.
PLoS biology
|July 6, 2023
概括
蝙蝠流感病毒使用主要基因相容性复合物II类 (MHC-II) 进行输入. 研究人员确定了特定的MHC-II域和保存的氨基酸,这些氨基酸对蝙蝠流感H18N11结合和广泛物种感染至关重要.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
背景情况:
- 流感A型病毒 (IAVs) 通常与化甘氨酸结合.
- 蝙蝠衍生的IAV与传统菌株不同,利用主要基因相容性复合物II类 (MHC-II) 进入宿主细胞.
- 蝙蝠IAV H18N11感染是由各种脊椎动物MHC-II分子支持的,但结合机制尚不清楚.
研究的目的:
- 为了阐明蝙蝠流感H18N11与MHC-II结合的分子基础.
- 为了确定特定的MHC-II域和残留物,对于H18N11介导的病毒入口至关重要.
主要方法:
- 使用人类白细胞抗原DR (HLA-DR) 和HLA-DM生成仿真MHC-II分子.
- 对H18:HLA-DR相互作用的结构建模.
- 在MHC-IIα2域内的关键氨基酸残留的局部定向突变发生.
主要成果:
- 病毒进入得到了HLA-DR/DM仿真体的支持,该仿真体包含HLA-DRα1,α2和β1域.
- 结构建模确定了HLA-DR α2域作为H18结合的核心.
- 突变分析确定了α2域 (N149,V190) 中保存的氨基酸对于H18N11输入至关重要.
结论:
- 特定域 (α1,α2,β1) 和在MHC-II分子中的保存残留物介于蝙蝠流感H18N11结合.
- 这些发现通过突出保存的MHC-II结合点来解释蝙蝠IAV的广泛物种热带性.
- 了解这种相互作用是研究蝙蝠流感病毒演变和传播的关键.
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