The Center for Microbes, Development and Health, Institut Pasteur of Shanghai-Chinese Academy of Sciences, Discovery and Molecular Characterization of Pathogens, Shanghai 200000, China.
ISEM, University of Montpellier, CNRS, EPHE, IRD, 34095 Montpellier, France.
Viruses. 2021 Jan 19;13(1):133. doi: 10.3390/v13010133.
Since the identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as the etiological agent of the current COVID-19 pandemic, a rapid and massive effort has been made to obtain the genomic sequences of this virus to monitor (in near real time) the phylodynamic and diversity of this new pathogen. However, less attention has been given to the assessment of intra-host diversity. RNA viruses such as SARS-CoV-2 inhabit the host as a population of variants called quasispecies. We studied the quasispecies diversity in four of the main SARS-CoV-2 genes (ORF1a, ORF1b, S and N genes), using a dataset consisting of 210 next-generation sequencing (NGS) samples collected between January and early April of 2020 in the State of Victoria, Australia. We found evidence of quasispecies diversity in 68% of the samples, 76% of which was nonsynonymous variants with a higher density in the spike (S) glycoprotein and ORF1a genes. About one-third of the nonsynonymous intra-host variants were shared among the samples, suggesting host-to-host transmission. Quasispecies diversity changed over time. Phylogenetic analysis showed that some of the intra-host single-nucleotide variants (iSNVs) were restricted to specific lineages, highlighting their potential importance in the epidemiology of this virus. A greater effort must be made to determine the magnitude of the genetic bottleneck during transmission and the epidemiological and/or evolutionary factors that may play a role in the changes in the diversity of quasispecies over time.
自严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 被确定为当前 COVID-19 大流行的病原体以来，人们已经做出了快速而大规模的努力来获得这种病毒的基因组序列，以监测（实时）这种新病原体的系统发育和多样性。然而，人们对宿主内多样性的评估关注较少。像 SARS-CoV-2 这样的 RNA 病毒在宿主中栖息为称为准种的变体群体。我们使用由 2020 年 1 月至 4 月初在澳大利亚维多利亚州收集的 210 个下一代测序 (NGS) 样本数据集，研究了 SARS-CoV-2 的四个主要基因（ORF1a、ORF1b、S 和 N 基因）中的准种多样性。我们在 68%的样本中发现了准种多样性的证据，其中 76%是非同义变体，在刺突 (S) 糖蛋白和 ORF1a 基因中的密度更高。大约三分之一的宿主内非同义变异在样本中共享，表明存在宿主间传播。准种多样性随时间而变化。系统发育分析表明，一些宿主内单核苷酸变异 (iSNVs) 局限于特定的谱系，突出了它们在该病毒流行病学中的潜在重要性。必须更加努力地确定在传播过程中遗传瓶颈的大小，以及可能在准种多样性随时间变化中起作用的流行病学和/或进化因素。
