在肠道病毒基因组中翻译启动的灵活性和调制
Rhian L O'Connor1, Georgia M Cook1, Jacqueline Hankinson1
1Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
PLoS pathogens
|February 9, 2026
概括
肠道病毒可以使用多个启动编码子来生产蛋白质,在人类细胞中提供竞争优势. 这项研究揭示了替代起始编码子如何影响病毒生存和基因表达.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 肠道病毒利用两个开放式读取框架 (ORF) 来进行蛋白质合成:上游蛋白 (UP) 和主多蛋白.
- 一些肠道病毒在正规病毒之外拥有额外的上游AUG (uAUG),可能作为替代的翻译启动地点.
研究的目的:
- 在肠道病毒转化中研究替代上游AUG编码子的功能意义.
- 确定这些替代启动地点对不同细胞模型中的病毒适应性的影响.
主要方法:
- 在CVA13的Coxsackievirus上采用了核糖体分析,以确定翻译启动事件.
- 记者系统被用来确认来自两个上游AUG的翻译.
- 对CVA13进行了突变性研究,以评估细胞系,有机体和神经系统中改变的上游AUG的表型影响.
主要成果:
- 规范和替代上游AUG编码子都用于感染细胞的翻译启动.
- 虽然额外的上游AUG中的突变没有影响不朽细胞系,但野生型病毒在人类肠道有机体和神经系统中表现出竞争优势.
- 修改较短的上游ORF的停止编码子导致其他ORF的翻译失调,表明其具有监管作用.
- 上游ORF转化受细胞应激反应的调节.
结论:
- 肠道病毒在内部核糖体进入部位 (IRES) 介导的启动中表现出显著的可塑性.
- 具有双重上游AUG的病毒在生理上相关的感染部位,如分化肠道器官和神经系统中具有竞争优势.
- 额外的上游ORF在调节其他病毒ORF的表达水平方面发挥着作用.
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