SARS-CoV-2 Omicron亚型逐渐适应人类细胞,通过改变宿主细胞进入细胞
Yasuteru Sakurai1,2,3, Sayaka Okada2, Takehiro Ozeki2,4
1Department of Emerging Infectious Diseases, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan.
mSphere
|August 27, 2024
概括
SARS-CoV-2的Omicron变种通过使用内体进入人体细胞来适应,与三角洲变种不同. 这种持续的适应影响了它的传染性和免疫逃避,影响了全球的感染.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 传染性疾病 传染性疾病
背景情况:
- 严重急性呼吸系统综合征冠状病毒2 (SARS-CoV-2) 持续演变,Omicron亚型显示出高传染性和免疫逃生.
- 了解新出现的SARS-CoV-2变种的病毒学特征对于预测感染和开发抗病毒策略至关重要.
研究的目的:
- 为了比较SARS-CoV-2 Omicron亚型 (BA.1-BA.5,BA.2.75,XBB/BQ) 与人类呼吸道和肠道细胞中的Delta变体的进入机制和细胞适应.
- 为了研究宿主细胞进入途径的进化变化和尖端蛋白质裂解的有效性.
主要方法:
- 在人体上/下呼吸道和肠道细胞模型中病毒进入和复制的体外分析.
- 对宿主细胞进入路径 (细胞表面与内体) 和蛋白酶依赖性的比较评估 (TMPRSS2与Cathepsin L).
- 在不同SARS-CoV-2变种中评估S1/S2尖端蛋白分裂效率.
主要成果:
- 与早期菌株相比,Omicron亚变种显示出增强的生长能力.
- 鼻上皮细胞支持某些类似于Delta的Omicron亚型的高效进入.
- 所有的Omicron变异都利用了内体内素L进入,不同于Delta的依赖细胞表面TMPRSS2.
- 最近的Omicron变种显示,与早期的Omicron尖峰相比,S1/S2尖峰切割效率有所改善.
结论:
- 这种Omicron变异通过内分体介导的进入逐渐适应人类细胞,这是跨子变异的保存机制.
- 改变宿主细胞进入途径和改善的尖裂解有助于Omicron亚变体的进化成功.
- 这项研究强调了SARS-CoV-2进化过程中既保留的,又不断变化的特征,特别是在宿主细胞相互作用方面.
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