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在慢性感染SARS-CoV-2患者中,宿主内部遗传多样性的不同模式

Adi Ben Zvi^1,2, Natalie Rutsinsky¹, Bar Jacobi^1,2

¹The Shmunis School of Biomedicine and Cancer Research, Tel Aviv University, George S. Wise Faculty of Life Sciences, Tel Aviv University, Chaim Levanon St, Tel Aviv-Yafo, 6997801, Israel.

Virus evolution

|July 15, 2025

概括

免疫功能低下个体的慢性SARS-CoV-2感染显示出多样化的病毒演变. 这项研究揭示了突变动态和宿主内部的基因组多样性,挑战了只从这些慢性感染中产生的关注变体 (VOCs) 的假设.

科学领域:

病毒学病毒学
基因组学就是基因组学.
免疫学免疫学免疫学

背景情况:

慢性SARS-CoV-2感染可能发生在严重免疫功能低下的个体中,病毒会在几个月内复制.
这些慢性感染中的适应性进化和突变固定类似于引起关注的变体 (VOCs) 中发现的变体,这导致了从慢性感染中出现VOCs的假设.

研究的目的:

在慢性感染期间调查SARS-CoV-2的突变动态和宿主内部基因组多样性.
为了区分真正的低频突变和测序错误.

主要方法:

来自9名患有慢性SARS-CoV-2感染的免疫功能低下个体的病毒基因组的纵向测序.
使用重复测序来区分测序错误和低频突变.
应用了通用线性模型来推断突变速率并分析进化动态.

主要成果:

确定了可能由于测序错误而导致的反复复发的低频突变,建立了可靠突变推断的严格方法.
推断出同名突变率为1.9 × 10-6 个突变/地点/天.
观察到患者特异的非同义分歧率,具有明显的异质性,表明各种选择压力和人口统计学历史塑造了宿主内病毒进化.
检测到高非同义率的发作,表明有选择性的扫描或亚种群替代.

结论:

慢性SARS-CoV-2感染中的宿主内部病毒演变非常多样化,并且与患者特定.
这些发现突出了选择压力和宿主内部动态在长期感染期间塑造病毒演变的复杂相互作用.
挑战了当前的假设,证明了不同的进化轨迹,而不是从慢性感染中出现的VOCs的统一出现途径.

关键词:

在 COVID-19 疫情中,这就是SARS-Coronavirus-2病毒.慢性感染慢性感染宿主内部进化的过程.

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