在免疫功能低下的患者中,在持续感染521天期间,SARS-CoV-2的适应性进化
Hanno Schmidt1,2,3, Lea Schick4, Jürgen Podlech5
1Sequencing Consortium, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany. hanno.schmidt@uni-mainz.de.
NPJ genomic medicine
|January 17, 2025
概括
在免疫功能低下的患者中,SARS-CoV-2病毒可以适应. 这项研究追踪了干细胞移植患者的特定变异 (BF.7.21),观察了尖端蛋白的显著突变,表明病毒进化.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 基因组学就是基因组学.
背景情况:
- 免疫功能低下的人面临着清除病毒感染的挑战.
- 持续的感染使病毒在宿主免疫系统内进化和适应.
- 严重急性呼吸系统综合征冠状病毒2 (SARS-CoV-2) 变种对公众健康构成重大关注.
研究的目的:
- 为了研究SARS-CoV-2在免疫功能低下患者中的基因组演变.
- 为了分析在异性造血干细胞移植后长期感染期间的病毒适应.
- 为了确定赋予潜在免疫逃避或改变病毒适应性的特定突变.
主要方法:
- 在五个不同的时间点从患者样本中对SARS-CoV-2的全基因组测序.
- 对病毒遗传变异的分析,包括氨基酸替代和删除.
- 在功能区域的突变频率的比较分析,特别是尖端蛋白的受体结合域 (RBD).
主要成果:
- 在免疫功能低下的患者中观察到长期的SARS-CoV-2感染 (521天) 与BF.7.21变种.
- 病毒群体在感染期间在编码区域积累了34个氨基酸替代和8个缺失.
- 在尖端蛋白的RBD中发现了11种氨基酸替代物,与随机分布相比是15倍的丰富,包括已知的耐药性相关突变 (例如K417T,L452Q,E484V).
结论:
- 观察到的突变模式强烈表明SARS-CoV-2在免疫受损宿主中正在进行的适应性进化.
- 在免疫功能低下的患者中,长期的病毒感染可能会导致显著的病毒遗传变化.
- 这些发现凸显了基因组监测对于了解病毒演变和潜在的治疗耐药性的重要性.
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