贝塔冠状病毒以不同的方式激活综合应激反应,以优化肺衍生细胞系中的病毒复制
David M Renner1,2, Nicholas A Parenti1,2, Nicole Bracci1,2
1Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Viruses
|January 25, 2025
概括
贝塔冠状病毒MERS-CoV和HCoV-OC43依赖eIF2α脱化进行复制. 然而,SARS-CoV-2似乎不敏感,并可能通过降低这一过程来限制宿主转换.
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:
- 包括MERS-CoV,HCoV-OC43和SARS-CoV-2在内的贝塔冠状病毒构成重大威胁.
- 类似PKR的ER激酶 (PERK) 途径是综合应激反应 (ISR) /未折叠蛋白质反应 (UPR) 的关键组成部分.
- 激活PERK会导致eIF2α的酸化和转化衰减.
研究的目的:
- 研究人类β冠状病毒与PERK通路之间的相互作用.
- 阐明eIF2α脱化在不同β冠病毒的病毒复制中的作用.
主要方法:
- 细胞感染了MERS-CoV,HCoV-OC43和SARS-CoV-2的病毒.
- 评估PERK通路激活和下游反应.
- 使用小分子抑制剂和基因操纵 (GADD34淘汰,CReP淘汰) 来研究eIF2α脱化.
主要成果:
- 这三种贝塔冠状病毒都激活了PERK和下游反应.
- 只有SARS-CoV-2在感染期间显示出可检测的p-eIF2α.
- 通过p-eIF2α脱化,MERS-CoV和HCoV-OC43的复制得到了增强.
- CReP的淘汰显著减少了HCoV-OC43的复制,而GADD34的废除的影响很小.
- 结合的GADD34淘汰和CReP淘汰对HCoV-OC43复制产生了最大的影响.
结论:
- eIF2α脱化对于MERS-CoV和HCoV-OC43蛋白质的产生和复制至关重要.
- SARS-CoV-2 似乎是不同的,可能会降低对脱酸化的调节,以抑制宿主转化.
- 贝塔冠状病毒对ISR/UPR通路的差异调节会影响病毒复制策略.
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