多重ACE2库的伪型病毒感染揭示了SARS-CoV-2变体在受体使用中的转移
Nidhi Shukla1, Sarah M Roelle1, John C Snell1
1Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America.
PLoS pathogens
|May 20, 2024
概括
病毒尖端蛋白进化改变了宿主受体的兼容性,影响了跨物种感染. 新变种与各种动物ACE2蛋白质的兼容性增加,突出显示了潜在的动物传播风险.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 基因组学就是基因组学.
背景情况:
- 宿主病毒蛋白相互作用对于感染结果至关重要.
- 宿主受体和病毒进入蛋白质的变化会影响敏感性.
- 病毒和宿主蛋白序列的组合空间复杂且不太了解.
研究的目的:
- 为评估病毒与宿主蛋白质的兼容性开发一种高通量测试.
- 为了研究SARS-CoV-2变体的尖端蛋白与ACE2的相互作用.
- 分析尖端蛋白的结构变化及其对宿主兼容性的影响.
主要方法:
- 使用多重宿主受体库开发了一个伪型病毒感染试验.
- 采用DNA条形码测序来同时读出感染.
- 测试了SARS-CoV-2和变体尖端蛋白与30个ACE2正统/突变.
主要成果:
- 像N501Y这样的SARS-CoV-2变种尖端突变导致了ACE2接口的显著结构变化.
- 这些结构变化改变了变异尖峰与各种动物ACE2正义词的兼容性.
- 在13个非人类ACE2正义体中的10个显示了变体特定的兼容性模式.
结论:
- 病毒尖峰序列演变可以动态地改变ACE2兼容性和动物感染潜力.
- 新兴变种可能与动物宿主具有更广泛的兼容性.
- 开发的试验为研究病毒与宿主蛋白相互作用提供了一个可扩展的方法.
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