蝙蝠SARS类冠状病毒RSSHC014和WIV1中尖端感染性的结构性决定因素
Shuyuan Qiao1,2,3, Xinquan Wang1,2,3
1The Ministry of Education Key Laboratory of Protein Science, Beijing, China.
Journal of virology
|July 19, 2024
概括
像rsSHC014和WIV1这样的蝙蝠冠状病毒 (CoV) 对人类的出现构成威胁. 对其尖端糖蛋白的结构分析揭示了病毒感染性和细胞进入的关键决定因素,包括Y623H替代.
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:
- 经常出现的冠状病毒 (CoV) 溢出影响对全球健康和经济构成重大风险.
- 蝙蝠CoV,特别是类似SARS的rsSHC014和WIV1,是人类出现的候选人,因为它们能够利用人类ACE2.
- 尖 (S) 糖蛋白对于CoV跨物种传播至关重要,它调解受体识别和膜融合.
研究的目的:
- 为了确定RSSHC014和WIV1 S糖蛋白的冷电子显微镜 (EM) 结构.
- 阐明WIV1 S蛋白与人类ACE2 (hACE2) 结合的结构基础.
- 调查调控蝙蝠SARS类型冠状病毒进入细胞效率和传染性的分子决定因素.
主要方法:
- 电子显微镜 (cryo-EM) 用于在封闭状态和中间状态中解析S蛋白结构.
- 确定WIV1 S-hACE2复合结构的确定.
- 生物化学分析和伪病毒感染实验.
- 位点定向突变发生,以确定病毒感染性的关键残留物.
主要成果:
- 冷EM结构揭示了rsSHC014和WIV1 S蛋白质的封闭和中间状态,具有动态变异.
- 在WIV1 S-hACE2复杂结构提供了关于人类受体结合的见解.
- 与WIV1相比,rsSHC014伪病毒显示细胞进入受损,尽管具有相似的ACE2结合亲缘关系.
- 在rsSHC014 S蛋白中的Y623H替代显著增强了伪病毒的细胞进入,可能是通过促进开放的S构造.
结论:
- 蝙蝠的类似SARS的冠状病毒rsSHC014和WIV1具有 hACE2介导细胞进入的内在能力.
- 有效的RBD"提升"和紧密的RBD-hACE2结合对于病毒感染至关重要.
- 在S糖蛋白的SD2区域中的623位点是蝙蝠SARS类CoV感染的关键决定因素,强调了其对潜在动物传染病事件的重要性.
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