在一个封闭的传播链中,免疫功能正常个体中的 SARS-CoV-2 群体动态显示出感染过程中的基因组多样性。

IF 10.4 1区 生物学 Q1 GENETICS & HEREDITY
Hannah Goldswain, Rebekah Penrice-Randal, I'ah Donovan-Banfield, Craig W Duffy, Xiaofeng Dong, Nadine Randle, Yan Ryan, Aleksandra M Rzeszutek, Jack Pilgrim, Emma Keyser, Simon A Weller, Emma J Hutley, Catherine Hartley, Tessa Prince, Alistair C Darby, Niall Aye Maung, Henry Nwume, Julian A Hiscox, Stevan R Emmett
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引用次数: 0

摘要

背景:SARS-CoV-2 仍在快速进化,许多具有重要生物学意义的基因组置换/嵌段已成为新的 SARS-CoV-2 世系的特征,这些新的 SARS-CoV-2 世系是在全球连续的大流行中出现的。全球范围内的基因组测序工作能够监测这些浪潮,追踪传播集群,并实时研究病毒的演变,从而为医疗保健政策提供依据。有一种观点认为,新出现的病毒系与当代变种的分化明显大于平均值,可能需要持续感染,例如在免疫力低下的宿主中感染。由于 COVID-19 大流行和采样的性质,很少有研究考察 SARS-CoV-2 在健康人体内的进化轨迹:方法:我们在一个封闭的传播链中调查了由 16 名感染 SARS-CoV-2 且无并发症的免疫功能健全者组成的群体中的病毒进化趋势和参与者的症状。通过纵向鼻咽拭子取样,可以在显性和次要基因组变异水平上通过 Nimagen-Illumina 测序分析 SARS-CoV-2 宿主内变异的特征:结果:在单个感染病例中观察到了病毒谱系的变化;然而,在急性感染期间只有一个吲哚,没有重组的迹象。不同参与者的次要和主要基因组修饰各不相同,一些次要基因组修饰的丰度增加,成为感染期间的主要病毒序列:结论:这批 SARS-CoV-2 感染者的数据表明,在免疫力低下的宿主中长期持续感染并不一定是产生高于平均频率的氨基酸替换的先决条件。在感染期间,在免疫功能正常的个体中观察到了显性和次要基因组序列水平上的氨基酸替换,这表明病毒系谱的变化会产生病毒多样性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
SARS-CoV-2 population dynamics in immunocompetent individuals in a closed transmission chain shows genomic diversity over the course of infection.

Background: SARS-CoV-2 remains rapidly evolving, and many biologically important genomic substitutions/indels have characterised novel SARS-CoV-2 lineages, which have emerged during successive global waves of the pandemic. Worldwide genomic sequencing has been able to monitor these waves, track transmission clusters, and examine viral evolution in real time to help inform healthcare policy. One school of thought is that an apparent greater than average divergence in an emerging lineage from contemporary variants may require persistent infection, for example in an immunocompromised host. Due to the nature of the COVID-19 pandemic and sampling, there were few studies that examined the evolutionary trajectory of SARS-CoV-2 in healthy individuals.

Methods: We investigated viral evolutionary trends and participant symptomatology within a cluster of 16 SARS-CoV-2 infected, immunocompetent individuals with no co-morbidities in a closed transmission chain. Longitudinal nasopharyngeal swab sampling allowed characterisation of SARS-CoV-2 intra-host variation over time at both the dominant and minor genomic variant levels through Nimagen-Illumina sequencing.

Results: A change in viral lineage assignment was observed in individual infections; however, there was only one indel and no evidence of recombination over the period of an acute infection. Minor and dominant genomic modifications varied between participants, with some minor genomic modifications increasing in abundance to become the dominant viral sequence during infection.

Conclusions: Data from this cohort of SARS-CoV-2-infected participants demonstrated that long-term persistent infection in an immunocompromised host was not necessarily a prerequisite for generating a greater than average frequency of amino acid substitutions. Amino acid substitutions at both the dominant and minor genomic sequence level were observed in immunocompetent individuals during infection showing that viral lineage changes can occur generating viral diversity.

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来源期刊
Genome Medicine
Genome Medicine GENETICS & HEREDITY-
CiteScore
20.80
自引率
0.80%
发文量
128
审稿时长
6-12 weeks
期刊介绍: Genome Medicine is an open access journal that publishes outstanding research applying genetics, genomics, and multi-omics to understand, diagnose, and treat disease. Bridging basic science and clinical research, it covers areas such as cancer genomics, immuno-oncology, immunogenomics, infectious disease, microbiome, neurogenomics, systems medicine, clinical genomics, gene therapies, precision medicine, and clinical trials. The journal publishes original research, methods, software, and reviews to serve authors and promote broad interest and importance in the field.
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