在肺细胞系中,对于SARS-CoV-2的内体和细胞表面进入所需的细胞糖分差是不同的
Kimberley C Siwak1, Emmanuelle V LeBlanc1, Heidi M Scott1
1Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Canada.
PLoS pathogens
|December 3, 2024
概括
细胞糖促进了SARS-CoV-2和相关病毒的内体体入口,但对于细胞表面入口来说并不必不可少. 这澄清了酸在病毒细胞进入途径中的作用.
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:
- 严重急性呼吸道冠状病毒-2 (SARS-CoV-2) 和其他冠状病毒 (CoV) 使用不同的细胞进入路径.
- 进入涉及尖端糖蛋白结合和膜融合,由细胞表面 (TMPRSS2-依赖) 或内体内 (素依赖) 的裂变引发.
- 在这些独特的Cov入境途径中,细胞糖的作用仍然不清楚.
研究的目的:
- 通过内体和细胞表面通路调查细胞酸糖对SARS-CoV-2和相关的萨尔贝科病毒进入的功能贡献.
- 为了比较不同冠状病毒入境途径中所需的酸甘及其对宿主蛋白酶 (如TMPRSS2和cathepsins) 的依赖.
主要方法:
- 基因和酶的消耗从细胞表面的酸.
- 使用各种sarbecoviruses (SARS-CoV-1,WIV1-CoV,WIV16-CoV,SARS-CoV-2变种) 的尖端蛋白质伪型的lentiviral颗粒.
- 在存在或不存在酸和在不同蛋白酶表达条件下 (TMPRSS2,cathepsins) 的CoV进入效率的比较.
主要成果:
- 进入SARS-CoV-1,WIV1-CoV,WIV16-CoV和SARS-CoV-2的Omicron变体需要内分体甲素和细胞血糖素.
- 祖先的SARS-CoV-2和Delta变种使用两种入口途径,但仅在TMPRSS2缺席时,需要酸才能进入内体.
- 酸不需要与SARS-CoV-2尖端蛋白结合或进入TMPRSS2-表达细胞,这表明它促进了内细胞的进入,而不是附着或融合.
结论:
- 细胞质甘对于SARS-CoV-2的附着,受体结合或融合并非必不可少,但特别促进了内细胞的进入.
- 对酸的要求因特定的冠状病毒,进入途径和宿主细胞蛋白酶表达而异.
- 结果澄清了sialoglycans调解内体,但不是细胞表面,进入SARS-CoV-2和相关的sarbecoviruses.
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