肝炎病毒的翻译需要PDGFA相关蛋白1,一个eIF4E结合蛋白调节内细胞网膜应激反应
Takayoshi Shirasaki1, Erik Lenarcic2, Ichiro Misumi3
1Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Science advances
|November 20, 2024
概括
甲型肝炎病毒使用独特的翻译机制,独立于细胞应激反应,确保病毒蛋白质合成. 这个过程依赖于PDAP1,这是一种对病毒和抗压宿主mRNA翻译至关重要的蛋白质.
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:
- 病毒蛋白错误折叠在内分泌网膜 (ER) 中可以诱导细胞应激.
- 这种压力通常会触发宿主反应,包括真核转化启动因子2亚单元α (eIF2α) 酸化.
- 甲型肝炎病毒 (HAV) 是一种正链RNA病毒,导致传染性肝炎.
研究的目的:
- 为了研究甲型肝炎病毒 (HAV) 在受感染的肝细胞中的转化机制.
- 要确定HAV是否使用依赖压力或独立翻译策略.
- 为了确定对HAV复制和抗压翻译至关重要的宿主因素.
主要方法:
- 在ER压力条件下对病毒蛋白合成的分析.
- 研究eIF2α酸化在HAV转化中的作用.
- 鉴定和描述血小板衍生生长因子亚单元A (PDGFA) 相关蛋白1 (PDAP1) 的功能.
- 评估PDAP1通过肝炎病毒内部核糖体进入部位 (IRES) 进行盖独立翻译的要求.
- 在小鼠模型中评估PDAP1对于生产性肝炎病毒感染的必要性.
主要成果:
- HAV采用一种抗ER应力且独立于eIF2α酸化的转化机制.
- PDAP1对于由肝炎病毒IRES驱动的帽子独立翻译至关重要.
- 在小鼠中,PDAP1对于生产性HAV感染至关重要.
- PDAP1与eIF1A相互作用,并促进对抗压力的宿主mRNA的翻译.
- 这些宿主mRNA编码有助于应激细胞生存的蛋白质.
结论:
- 甲型肝炎病毒已经发展出一种复杂的,抗压的翻译策略,以确保病毒蛋白质的生产.
- 在ER压力期间,PDAP1是关键的宿主因子,可以实现病毒复制和特定宿主生存mRNA的翻译.
- 了解PDAP1的作用提供了对病毒病原和细胞应激适应的见解.
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