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在病毒演化过程中,SARS-CoV-2受体结合领域的突变约束

Tyler N Starr¹, Allison J Greaney^1,2,3, William W Hannon^1,4

¹Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

Science (New York, N.Y.)

|June 28, 2022

概括

SARS-CoV-2 变种通过尖端蛋白的受体结合域 (RBD) 的突变演变. 这些变化受到表皮病的影响,塑造了病毒的进化和抗体逃逸,影响了像Omicron这样的未来菌株.

科学领域:

病毒学
分子生物学
遗传学

背景情况:

严重急性呼吸综合征冠状病毒2 (SARS-CoV-2) 变种表现出尖端受体结合域 (RBD) 替代,影响了ACE2结合和抗体识别.
这些替代物可能会通过表皮病影响未来的病毒进化,其中某个部位的突变会改变其他部位的突变效应.

研究的目的:

调查表皮病在塑造SARS-CoV-2演变中的作用.
测量各种SARS-CoV-2变种 (武汉-胡-1,阿尔法,贝塔,德尔塔,埃塔) 的RBD中所有单氨基酸突变对ACE2结合的影响.

主要方法:

使用深度突变扫描来评估特定SARS-CoV-2变异的RBD中所有单氨基酸替代的影响.
分析的重点是对人类血管素转化酶2 (ACE2) 受体的结合 afinity 的变化.

主要成果:

特定的替代物,特别是Asn501Tyr (N501Y),诱导了表皮转移,改变了其他部位的突变效应.
观察到这些表观变化促进了随后的进化变化,包括在Omicron变异中看到的抗体逃生突变.
尽管保持了RBD的整体结构,但表性影响是明显的.

结论:

在SARS-CoV-2的进化轨迹中,表皮症起着至关重要的作用,影响了具有改变结合性和免疫逃逸性特性的变种的出现.
了解RBD中的这些序列功能关系对于解释正在进行的病毒演变和预测未来的SARS-CoV-2适应性至关重要.

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