深度突变,插入和删除扫描整个肠道病毒A蛋白质组揭示了塑造病毒进化的约束
William Bakhache1, Walker Symonds-Orr1, Lauren McCormick1,2
1Quantitative Virology and Evolution Unit, Laboratory of Viral Diseases, NIH-NIAID Division of Intramural Research, Bethesda, MD, USA.
Nature microbiology
|November 28, 2024
概括
插入和删除 (InDels) 对病毒蛋白的进化至关重要. 这项研究绘制了Enterovirus A71中InDel耐受性的地图,揭示了少数热点,其中一些与宿主相互作用有关,表明它们在病毒多样化中的作用.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 蛋白质进化 蛋白质进化
背景情况:
- 插入和删除 (InDels) 对蛋白质进化和病毒适应至关重要.
- 在RNA病毒中,InDels可以导致新的表型,改变宿主相互作用和热带性.
- 病毒蛋白质组对InDels的耐受性在很大程度上仍未被描述.
研究的目的:
- 为了全面地绘制和量化完整的病毒蛋白质组对插入,删除和替代的突变耐受性.
- 为了在肠道病毒A71蛋白质组中识别耐受InDels的特定位点.
主要方法:
- 使用深度突变扫描来评估遗传变异的影响.
- 大约有45,000个插入,6,000个删除和41,000个氨基酸替代在 enterovirus A71蛋白质组中进行了工程设计.
- 人口测序被用来量化这些突变对病毒健康状况的影响.
主要成果:
- 大多数InDels被发现对病毒具有致命性.
- 只有有限数量的"热点"显示对InDels.的耐受性.
- 其中一些耐受InDel的热点与参与宿主识别和免疫参与的区域重叠.
结论:
- 病毒蛋白质体对InDels的耐受性有限,耐受性集中在特定的部位.
- 鉴定到的热点表明,InDels在过去Enterovirus A71.1的表型多样化中发挥了重要作用.
- 了解InDel耐受性提供了对病毒进化和适应机制的见解.
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