-eIF4E刺激通过选择性表达细胞膜居住因子来调节冠状病毒的进入
Xiu-Zhong Zhang1, Jing Wang1, Wen-Jun Tian1
1National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Journal of virology
|February 1, 2024
概括
化真核转化启动因子eIF4E (p-eIF4E) 通过上调宿主因子TSPAN3,CD63和ITGB2.2来促进PEDV病毒的进入. 这通过ERK-MNK途径发生,影响病毒生命周期.
科学领域:
- 分子生物学分子生物学
- 病毒学 病毒学
- 细胞生物学 细胞生物学
背景情况:
- 细胞翻译启动因子eIF4E通过酸化在氨酸209处调节细胞翻译.
- 以前的研究表明,化eIF4E (p-eIF4E) 影响了参与信号通路的特定mRNA的翻译.
- 对于p-eIF4E在病毒感染中的作用,特别是对于宿主细胞因子,需要进一步阐明.
研究的目的:
- 调查p-eIF4E与影响猪流行性腹病毒 (PEDV) 的下游宿主细胞蛋白之间的关系.
- 通过p-eIF4E.确定参与PEDV入侵的特定宿主因素及其调节.
- 为了阐明在PEDV感染期间负责eIF4E酸化的信号通路.
主要方法:
- 定量蛋白质组学 (TMT) 用于识别受p-eIF4E影响的蛋白质.
- 耗尽研究 (siRNA) 和抗体阻断,以评估宿主因子 (TSPAN3,CD63,ITGB2) 在病毒进入中的作用.
- 在细胞培养和小猪中分析PEDV感染后的eIF4E酸化和宿主因子表达.
- 使用S209A-Vero细胞 (非酸化eIF4E) 和MNK激酶抑制剂来研究eIF4E酸化和ERK-MNK通路的作用.
主要成果:
- TSPAN3,CD63和ITGB2的耗尽显著抑制了PEDV入侵和伪型病毒颗粒的进入 (PEDV-pp,SARS-CoV-pp,SARS-CoV-2-pp).
- 对TSPAN3,CD63和ITGB2的抗体阻止了PEDV吸附.
- PEDV感染增加了eIF4E酸化和TSPAN3,CD63和ITGB2在翻译水平上的表达.
- 非酸化eIF4E (S209A-Vero细胞) 减少了PEDV病毒入侵,MNK抑制阻止了PEDV的进入和宿主因子积累.
- 确定ERK-MNK通路是PEDV诱导的eIF4E酸化的原因.
结论:
- p-eIF4E刺激了膜居住宿主因子TSPAN3,CD63和ITGB2的表达,促进了PEDV的进入.
- ERK-MNK通路调解PEDV诱导的eIF4E酸化,从而在转化层面上调节这些宿主因子.
- TSPAN3,CD63和ITGB2对于多种冠状病毒的进入至关重要,包括SARS-CoV,SARS-CoV-2和HCoV-OC43.
- 这项研究揭示了p-eIF4E与病毒感染必不可少的宿主因子之间的新鲜联系,扩大了对eIF4E在病毒生命周期中的作用的理解.
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