对XBB.1.5和BQ.1.1的深度突变扫描显示,在SARS-CoV-2进化过程中,正在进行的表观性漂移
Ashley L Taylor1, Tyler N Starr1
1Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
bioRxiv : the preprint server for biology
|September 25, 2023
概括
SARS-CoV-2 的演变通过持续的表观漂移继续,影响病毒突变和受体结合. 最近的变种显示的变化比Omicron少,但像EG.5中的F456L这样的突变标志着未来的进化方向.
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:
- 突变影响对方影响的表观性,塑造了病毒进化.
- 之前的研究发现了显著的表观转移,如N501Y,推动了SARS-CoV-2 Omicron的早期出现.
- 目前对当前SARS-CoV-2变种持续的表观性影响的程度仍在调查中.
研究的目的:
- 研究SARS-CoV-2尖端受体结合域 (RBD) 中突变和缺失对ACE2结合和蛋白质表达的影响.
- 为了比较最近的Omicron变种 (BQ.1.1,XBB.1.5) 与早期菌株的突变模式.
- 了解表皮病在指导SARS-CoV-2正在进行的演变中的作用.
主要方法:
- 在RBD中对所有单个氨基酸替代和单个codon缺失进行深度突变扫描.
- 对每个突变/缺失的ACE2结合亲和力和蛋白质表达的测量.
- 在不同的SARS-CoV-2变种中对突变景观的比较分析.
主要成果:
- 许多突变被容忍或增强最近的变体中的ACE2结合.
- 在RBD中删除通常是可以容忍的,其中一些与更广泛的萨尔贝科病毒内区变异保持一致 (例如,BA.2.86中的Δ483).
- 最近的替代物比N501Y引起的表皮性转移不那么剧烈,但持续的漂移是显而易见的,相互作用影响了453,455和456等位点 (例如EG.5中的F456L).
结论:
- SARS-CoV-2 的进化特点是持续的表皮性漂移,微妙地改变突变效应.
- 虽然主要的表皮盐变不那么明显,但累积漂移会影响未来的进化轨迹.
- 了解这些表观相互作用对于预测新型SARS-CoV-2变种的出现至关重要.
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