动氨酸独立内细胞分裂是一种多种动物病毒的替代细胞进入机制
Ravi Ojha1, Anmin Jiang2, Elina Mäntylä3
1Department of Virology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
PLoS pathogens
|November 14, 2024
概括
动氨酸 (Dyn) 对于单受体病毒通过受体介导内细胞分裂 (RME) 进入至关重要. 虽然对于一些病毒至关重要,但dynamin提高了多受体病毒的吸收效率,这些病毒也利用actin网络感染.
科学领域:
- 细胞生物学 细胞生物学
- 病毒学 病毒学
- 分子生物学分子生物学
背景情况:
- 受体介导内细胞分裂 (RME) 对于细胞吸收各种分子和病原体至关重要.
- 动氨酸 (Dyn),一个大型的GTPase,在RME期间在囊泡分裂中起着关键作用.
- 之前关于激素在病毒进入中的作用的研究受限于基因和药理工具的非目标效应.
研究的目的:
- 调查动胺异型体在病毒进入途径中的关键性和贡献.
- 阐明动胺在具有单个或多个受体的病毒吸收中的作用.
- 了解激素在SARS-CoV-2进入中的作用,特别是关于TMPRSS2和病毒变异.
主要方法:
- 利用了条件遗传淘汰 (KO) 的小鼠胚胎纤维细胞,缺少所有三种动胺异型 (Dyn-KO-MEF).
- 感染了各种病毒的Dyn-KO-MEF和野生型MEF,包括犬类帕维病毒和SARS-CoV-2.
- 在TMPRSS的存在或不存在下,评估病毒进入效率和对动氨酸和动氨酸的依赖2.2.
主要成果:
- 小型病毒,如犬类帕尔沃病毒,严格要求输入dynamin.
- 较大的病毒和使用多个受体的病毒感染Dyn-KO-MEF的效率较低,但仍然是可行的.
- 在没有TMPRSS2的情况下,SARS-CoV-2的入口依赖于dynamin和actin;与武汉菌株相比,Omicron变种显示TMPRSS2依赖性减少.
结论:
- 对于依赖单个受体进入的病毒来说,激素是必不可少的.
- 动氨酸不是必不可少的,但增强了多受体病毒的效率,这些病毒也依赖于actin.
- 动氨酸在病毒进入中的作用因病毒特征和宿主细胞因素 (如TMPRSS2表达) 而有所不同.
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