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通过深度插入和删除扫描揭示Enterovirus A的结构可塑性

William Bakhache¹, Walker Orr¹, Lauren McCormick^1,2

¹Quantitative Virology and Evolution Unit, Laboratory of Viral Diseases, NIH-NIAID Division of Intramural Research, Bethesda, MD, USA.

Research square

|February 27, 2024

概括

插入和删除 (InDels) 通过改变蛋白质功能来驱动病毒进化. 这项研究绘制了Enterovirus A71中的InDel耐受性,揭示了对病毒物种化和潜在疫苗标至关重要的灵活区域.

科学领域:

病毒学病毒学
分子生物学分子生物学
进化生物学进化生物学

背景情况:

插入和删除 (InDels) 是蛋白质新性和病毒进化的关键驱动因素.
在RNA病毒中,InDels可以导致显著的表型变化,影响免疫逃避和宿主相互作用.

研究的目的:

为了探索RNA病毒对InDels的突变耐受性.
为了全面地绘制整个肠道病毒A71 (EV-A71) 蛋白质组的InDels的健身效应.
为了确定Enterovirus A物种内进化能力的区域.

主要方法:

通过使用深度InDel扫描,在EV-A71蛋白质组中设计了大约45,000个插入和6,000个删除.
量化了每个InDel对病毒健康的影响.
对EV-A物种进行了植物遗传学分析,以将实验发现与自然进化相关联.

主要成果:

大多数InDels对病毒健康有害,经常被证明是致命的.
在病毒蛋白质组中确定了特定的INDEL耐受区域.
这些耐受性位点与结构灵活和突变塑性蛋白质区域相对应,避免了必不可少的结构/功能元素.
在EV-A物种中,InDels的实验热点与自然存在的InDel地点重叠.

结论:

InDels通过利用结构性塑性区域在肠道病毒物种化中发挥着重要作用.
已确定的耐受InDel的区域代表了需要监测的进化能力的区域.
这些发现可能有助于开发新型肠道病毒疫苗.

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