通过TMPRSS2介导的SARS-CoV-2吸收增强了先天性免疫激活,增强了细胞病理学,并推动了融合的病毒进化
Bingqian Qu1,2, Csaba Miskey3, André Gömer4
1Division of Veterinary Medicine, Paul-Ehrlich-Institut, 63225 Langen, Germany.
概括
跨膜蛋白酶血清2 (TMPRSS2) 促进SARS-CoV-2的进入,增加病毒复制和宿主免疫反应. 这种增强的细胞进入会影响病毒突变选择和宿主细胞死亡,对动物感染的储存库有影响.
科学领域:
- 病毒学 病毒学
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 跨膜蛋白酶血清2 (TMPRSS2) 促进严重急性呼吸系统综合征冠状病毒2 (SARS-CoV-2) 进入宿主细胞.
- 对于TMPRSS2-介导增强进入对病毒和宿主细胞过程的确切影响尚不完全理解.
研究的目的:
- 研究TMPRSS2-介导的SARS-CoV-2进入如何影响下游病毒复制,宿主反应和病毒进化.
- 探索TMPRSS2在不同SARS-CoV-2变种的病毒吸收效率中的作用及其在哺乳动物储库中的更广泛意义.
主要方法:
- 使用具有或没有TMPRSS2联合表达的工程细胞进行感染测定.
- 电子显微镜和抑制剂实验用于研究病毒内部化途径.
- 转录分析分析宿主抗病毒和炎症反应.
- 基因组分析以确定与细胞进入效率相关的病毒突变.
主要成果:
- TMPRSS2通过内分体增强SARS-CoV-2的内部化,部分依赖于克拉斯林介导的内分细胞.
- 增加吸收效率可以促进病毒复制,转录,分泌和宿主抗病毒反应,从而产生变种特定的结果.
- 增强TMPRSS2的感染导致细胞病变,亡,亡和Nsp3的融合病毒突变增加,从而产生干扰素对抗性.
- 哺乳动物TMPRSS2的正方体也增强了泛变型的SARS-CoV-2的吸收.
结论:
- TMPRSS2通过将细胞进入效率与先天性免疫激活,细胞死亡和病毒进化联系起来,显著影响SARS-CoV-2生命周期.
- 这些发现凸显了TMPRSS2在SARS-CoV-2病变发生过程中的关键作用,以及其在动物传播和动物模型中的重要性.
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