Pleitotropic 对功能和稳定性的突变影响限制了流感血质素的抗原演变
Timothy C Yu1,2, Caroline Kikawa1,3,4, Bernadeta Dadonaite1
1Division of Basic Sciences and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Nature ecology & evolution
|December 1, 2025
概括
突变之间的相互作用影响流感病毒的进化. 虽然它使免疫逃生突变成为可能,但它无法克服稳定性问题,限制病毒进化.
科学领域:
- 病毒学 病毒学
- 进化生物学 进化生物学
- 分子生物学分子生物学
背景情况:
- 人类流感病毒血质素 (HA) 进化需要平衡免疫逃脱与蛋白质功能和稳定性.
- 突变效应取决于遗传背景的表观症 (epistasis) 复杂化了对这些进化约束的理解.
研究的目的:
- 为了研究表皮病在调解免疫逃脱和H3N2流感HA中的蛋白质功能/稳定性之间的类冲突中的作用.
- 确定氨基酸突变如何影响HA的细胞进入,酸稳定性和抗体中和.
主要方法:
- 对人类H3N2流感菌株HA中所有单个氨基酸突变的系统测量.
- 评估突变对HA介导细胞进入的影响.
- 评估突变对HA酸稳定性的影响.
- 通过人血清抗体量化中和.
主要成果:
- 表观症已经根深蒂固了某些突变,使得祖先的氨基酸身份无法生存.
- 表观症促进了以前有害的抗原突变的出现.
- 表观症不足以克服降低稳定性的抗原突变,解释了它们有限的固定性.
结论:
- 表观症在塑造H3N2流感的演变中发挥着重要作用,通过使抗原变化成为可能.
- 类效应,特别是蛋白质稳定性,对流感演变轨迹施加限制.
- 了解表观症和表观症对于预测流感病毒适应和免疫逃避策略至关重要.
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