全尖深度突变扫描有助于预测SARS-CoV-2细胞群的进化成功
Bernadeta Dadonaite1, Jack Brown2, Teagan E McMahon1
1Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, Washington, 98109, USA.
bioRxiv : the preprint server for biology
|November 28, 2023
概括
SARS-CoV-2的尖端突变会影响免疫逃逸和病毒健康. 了解这些变化,特别是受体结合域之外的变化,有助于预测未来的病毒进化和开发有效的对策.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 严重急性呼吸系统综合征冠状病毒2 (SARS-CoV-2) 变种积累了尖端蛋白突变.
- 这些突变影响病毒适应性,包括免疫逃避,ACE2受体结合和细胞进入.
- 了解突变效应对于预测病毒演变至关重要.
研究的目的:
- 研究SARS-CoV-2 XBB.1.5和BA.2尖端蛋白中的9000多个突变如何影响ACE2结合,细胞进入和血清介导的免疫逃生.
- 为了将尖端蛋白突变效应与观察到的病毒类成长率相关联.
主要方法:
- 伪病毒深度突变扫描被用于评估>9000个尖端突变.
- 测试测量了ACE2结合,病毒进入细胞和被人血清中和的中和.
- 在SARS-CoV-2进化和病毒适应性背景下分析了突变效应.
主要成果:
- 受体结合域 (RBD) 外的突变显著影响ACE2结合.
- 在RBD (位点357,420,440,456,473) 中发现了最强的血清脱离突变,具有可变的抗原影响.
- 在RBD之外发现了脱离突变,一些通过调节RBD构造来降低ACE2结合.
结论:
- 在RBD之外的尖端蛋白突变在病毒进化和ACE2结合中起着重要作用.
- 该研究提供了对免疫逃避机制和潜在的病毒适应性的见解.
- 测量到的尖峰表型与病毒生长率相关,使得可以更好地预测SARS-CoV-2的演变.
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