宿主细胞蛋白质组中由汉塔病毒核囊蛋白调节
Austin Royster1, Songyang Ren1, Saima Ali1
1Western University of Health Sciences, Pomona, California, United States of America.
PLoS pathogens
|January 8, 2024
概括
汉塔病毒核体蛋白 (NP) 通过上调含有瓦洛辛蛋白 (VCP/p97) 的翻译来劫持宿主细胞机械. 这种相互作用通过控制VCP水平并促进病毒颗粒的释放来增强病毒复制和传播.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 汉塔病毒采用独特的翻译策略来增强宿主细胞中的病毒mRNA表达.
- 汉塔病毒核蛋白 (NP) 与核糖体子单元和病毒mRNA相互作用,以促进翻译.
- 在NP上调节参与蛋白质加工的特定宿主细胞因子,包括含有瓦洛的蛋白质 (VCP/p97).
研究的目的:
- 研究汉塔病毒NP增强宿主细胞因子翻译的机制.
- 阐明含瓦洛辛蛋白 (VCP/p97) 在汉塔病毒复制和传播中的作用.
- 了解汉塔病毒如何操纵VCP mRNA转化,使其受益.
主要方法:
- 在体外和基于细胞的转化试验中使用记者构造.
- 对VCP/p97 mRNA 5' UTR与多个上游开始编码子的分析.
- 共同免疫沉以研究VCP-hantavirus糖蛋白相互作用.
- 进行VCP淘汰实验,并评估病毒颗粒的产生和退出.
- 对VCP mRNA 5' UTR.的NP结合试验.
主要成果:
- 汉塔病毒NP与VCP mRNA 5' UTR结合,特别是在上游开始编码子 (542nd AUG) 附近.
- NP结合抑制了5' UTR中短的翻译,从而促进了全长VCP的翻译.
- VCP的淘汰减少了传染性汉塔病毒颗粒的产生和输出.
- VCP与汉塔病毒糖蛋白 Gn 相互作用,促进病毒传播.
结论:
- 汉塔病毒利用VCP mRNA 5' UTR调节机制来增加感染细胞中的VCP水平.
- 升高的VCP水平对于有效的汉塔病毒复制,粒子释放和细胞间传播至关重要.
- NP,VCP和病毒糖蛋白之间的相互作用是汉塔病毒生命周期的关键.
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