探索SARS-CoV-2Omicron变异的Syndekan介导的细胞内化过程
Annamária Letoha1, Anett Hudák2, Tamás Letoha2
1Department of Medicine, Albert Szent-Györgyi Clinical Center, Faculty of Medicine, University of Szeged, 6720 Szeged, Hungary.
International journal of molecular sciences
|September 28, 2023
概括
像Omicron这样的SARS-CoV-2变种越来越多地使用硫酸肝 (HS) 和合成 (SDC) 进入细胞. 这就是Omicron.
科学领域:
- 病毒学 病毒学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 严重急性呼吸系统综合征冠状病毒2 (SARS-CoV-2) 变种表现出改变的细胞进入机制.
- 肝素硫酸盐 (HS) 蛋白质甘氨酸 (HSPG) 和合成甘氨酸 (SDC) 在病毒附着和感染中起作用.
- 之前的研究表明,与野生型 (WT) 的SARS-CoV-2相比,Delta变种增强了HS结合.
研究的目的:
- 为了比较WT SARS-CoV-2,Delta和Omicron变种的ACE2-和SDC-依赖的细胞吸收.
- 研究Omicron利用的主要细胞进入途径,重点关注HS/HSPG依赖性.
主要方法:
- 使用过度表达ACE2或SDC的细胞模型.
- 通过使用热不活化的病毒颗粒进行了内部化研究.
- 在SDC4敲除 (KD) 和用肝素治疗后评估病毒吸收率.
主要成果:
- 由于ACE2过度表达,Omicron变异的内部化没有得到补偿,这表明主要依赖HSPG.
- SDCs增强了所有三种病毒的内部化,观察到不同的SDC异型偏好.
- 奥米克龙在SDC4 KD和肝素抑制时显示出最显著的吸收减少,突出显示其强烈的HSPG亲和力.
结论:
- 奥米克龙主要使用HSPG,特别是SDC4,进行蜂入口.
- 依赖于普遍表达的SDC4可能有助于Omicron的高效传播.
- 奥米克朗的特定进入机制可能与其观察到的降低病原性相关.
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