在蝙蝠和人类细胞中的冠状病毒蛋白相互作用映射识别了免疫逃避和复制的分子和遗传开关
bioRxiv : the preprint server for biology
|August 6, 2025
概括
在SARS-CoV-2的核囊蛋白中发生的单一突变使其能够在蝙蝠细胞中复制. 这种变化也影响了病毒蛋白Orf9b的相互作用,影响了蝙蝠与人类的免疫逃避和宿主适应.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 宿主-病原体相互作用
背景情况:
- 像SARS-CoV-2这样的冠状病毒会导致严重的人类疾病,但蝙蝠仍然是无症状的水库.
- 了解病毒-宿主蛋白-蛋白相互作用 (PPI) 对于解释这种差异至关重要.
研究的目的:
- 在人类和蝙蝠细胞中比较SARS-CoV-2和RaTG13的PPI地图.
- 为了确定调节病毒感染动态和适应的宿主特异性相互作用.
主要方法:
- 使用亲和性净化质谱法 (AP-MS) 生成比较PPI地图.
- 使用的人类和 *Rhinolophus ferrumequinum* (RFe) 蝙蝠细胞系.
- 分析了病毒蛋白Orf9b与线粒体蛋白的相互作用.
主要成果:
- 鉴定了影响感染的保存,病毒特异和宿主特异的PPI.
- SARS-CoV-2 需要核突变才能在表达人类 ACE2/TMPRSS2 的蝙蝠细胞中复制.
- 在Orf9b的单个残留物差异改变了与Tom70 (人类细胞) 和MTARC2 (蝙蝠细胞) 的相互作用.
结论:
- 在Orf9b中,单个氨基酸替代重新塑造了病毒与宿主之间的相互作用,影响了免疫逃避.
- 这种残留物变化增强了与蝙蝠特定限制因子的相互作用,有助于宿主适应.
- 宿主特异性PPI和单残留变异是冠状病毒宿主热带性和病原性的关键决定因素.
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