SARS-CoV-2非结构性蛋白6从阿尔法到Omicron:一个跨膜蛋白质的演变
Shuchen Feng1, Amornrat O'Brien1, Da-Yuan Chen2,3
1Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago , Chicago, Illinois, USA.
mBio
|July 21, 2023
概括
在SARS-CoV-2非结构性蛋白6 (nsp6) 缺失中的突变在多个变异中被独立选择. 这些nsp6删除可能代表人类复制的适应,影响冠状病毒的病原性.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 基因组学就是基因组学.
背景情况:
- 在SARS-CoV-2尖端糖蛋白和非结构蛋白6 (nsp6) 中的突变与Omicron BA.1衰减有关.
- 尽管它在病毒RNA复制中的重要功能,但nsp6突变在病毒病原发生的确切作用仍然不清楚.
- Nsp6修改了细胞内膜网膜以产生双膜囊泡,这对于病毒RNA复制至关重要.
研究的目的:
- 为了研究SARS-CoV-2中nsp6突变的进化轨迹.
- 为了确定nsp6删除是否在不同的SARS-CoV-2血统中被独立选择.
- 探索nsp6删除作为适应人类宿主的潜在作用.
主要方法:
- 分析了91596个高可信度的人类SARS-CoV-2全基因组序列,跨越了19个变体和谱系.
- 在蝙蝠和松鼠中对来自SARS-CoV-2相关的冠状病毒的nsp6序列进行比较分析.
- 基于多个冠状病毒的序列nsp6的结构建模.
主要成果:
- 早期的SARS-CoV-2变种 (Alpha,Beta,Gamma) 在nsp6.6中表现出三重氨基酸删除 (ΔSGF).
- 德尔塔,埃普西隆和穆血统保留了祖先的nsp6序列.
- 奥米克朗BA.1显示氨基酸缺失 (ΔLSG),而BA.2和随后的奥米克朗系主要具有ΔSGF缺失.
- 蝙蝠和松鼠冠状病毒中的Nsp6序列与祖先的SARS-CoV-2 nsp6相似,这表明人类的特定适应性.
- 结构分析预测nsp6是一种多通的跨膜蛋白,具有保留的C端域.
结论:
- 在整个大流行期间,Nsp6删除在多个SARS-CoV-2血统中被独立选择.
- 观察到的nsp6删除可能是适应人类宿主.
- 了解nsp6进化有助于理解大流行冠状病毒的衰减.
- 对于NSP6在病变发生中的作用,需要对现有和新出现的冠状病毒进行进一步的研究.
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