SARS-CoV-2 非结构性蛋白3和4的表达可以调整细胞培养中展开的蛋白质反应
Jonathan P Davies1, Athira Sivadas1, Katherine R Keller2
1Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37240, United States.
Journal of proteome research
|December 1, 2023
概括
在SARS-CoV-2中,nsp4和nsp3.1非结构性蛋白调节宿主.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 细胞应激反应的应激反应
背景情况:
- 冠状病毒 (CoV),包括SARS-CoV-2,可以操纵宿主蛋白质稳定.
- 展开的蛋白质反应 (UPR) 是冠状病毒准的关键压力途径.
- 病毒非结构蛋白 (nsps) 在UPR调节中的作用基本上是未知的.
研究的目的:
- 调查SARS-CoV-2 nsp4对UPR的影响.
- 确定nsp3.1和nsp4如何合作来规范UPR.
- 为了阐明在SARS-CoV-2感染期间UPR激活的时间动态.
主要方法:
- 在细胞培养中过度表达SARS-CoV-2 nsps.
- 定量蛋白质组学用于分析UPR效应蛋白.
- 对nsp3.1和nsp4的同表达研究.
- 重新分析SARS-CoV-2感染蛋白质组学数据.
主要成果:
- SARS-CoV-2 nsp4优先激活UPR的ATF6和PERK分支.
- Nsp3.1可以抑制nsp4介导的PERK激活,但不能抑制ATF6激活.
- SARS-CoV-2 感染显示了依赖时间的 PERK 目标激活,随着时间的推移而消失.
结论:
- 在SARS-CoV-2感染期间,NSP3和NSP4在调整PERK通路方面发挥着作用.
- 通过nsps对PERK的时间调节可能会减弱病毒复制的宿主翻译.
- 这项研究强调了用于分析CoV与宿主相互作用和UPR调制的蛋白质学方法.
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