在SARS-CoV-2核体中的变异突变通过改变的基因组封装增强了病毒感染
Hannah C Kubinski1, Hannah W Despres1, Bryan A Johnson2,3,4
1Department of Microbiology and Molecular Genetics, Robert Larner, M.D. College of Medicine, University of Vermont, Burlington VT, 05405, USA.
bioRxiv : the preprint server for biology
|April 1, 2024
概括
核体蛋白中的Delta变异突变 (G215C) 产生二硫化键,形成稳定的二元体. 这种突变在体外和体内显著增强了严重急性呼吸系统综合征-冠状病毒-2 (SARS-CoV-2) 的病毒生长.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- SARS-CoV-2 变种的演变凸显了了解个别突变及其表型影响的重要性.
- 在Spike蛋白之外的突变研究较少,但整个病毒基因组处于进化选择之下.
- 核体 (N) 蛋白质的中心无序链接区域是显著进化压力的地点.
研究的目的:
- 调查SARS-CoV-2核体蛋白中突变的功能影响,特别是在三角洲变种中发现的G215C突变.
- 确定G215C突变在核蛋白二元化中的作用及其对病毒复制的影响.
- 分析N-N二聚体形成对病毒粒子组装和形态学的后果.
主要方法:
- 鉴定SARS-CoV-2Delta变异的核体 (N) 蛋白中的G215C突变.
- 使用反向遗传学将G215C突变引入WA1 SARS-CoV-2背景.
- 在体外和体内评估病毒生长动力学.
- 使用电子显微镜或类似技术分析核囊包装和病毒体形态.
主要成果:
- G215C突变引入了氨酸残留物,通过二硫化键形成稳定的N-N二聚体.
- 这种半氨酸残留物既必要又足以形成稳定的二元体.
- 与野生类型相比,N:G215C病毒在体外和体内显著增加病毒生长.
- 含有N:G215C突变的病毒包装了更多的核体,并显示出更大,更长的形态.
结论:
- 在SARS-CoV-2核体蛋白中的G215C突变驱动稳定的二分体形成,增强病毒复制.
- N-N二元形成影响病毒组合,导致核囊包装增加和病毒结构改变.
- 了解这些核囊蛋白的动态,可以了解SARS-CoV-2的进化和病变.
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