PDF(Pubmed)
Abstract：
UNASSIGNED: SARS-CoV-2 isolates of a given clade may contain low frequency genomes that encode amino acids or deletions which are typical of a different clade.
UNASSIGNED: Here we use high resolution ultra-deep sequencing to analyze SARS-CoV-2 mutant spectra.
UNASSIGNED: In 6 out of 11 SARS-CoV-2 isolates from COVID-19 patients, the mutant spectrum of the spike (S)-coding region included two or more amino acids or deletions, that correspond to discordant viral clades. A similar observation is reported for laboratory populations of SARS-CoV-2 USA-WA1/2020, following a cell culture infection in the presence of remdesivir, ribavirin or their combinations. Moreover, some of the clade-discordant genome residues are found in the same haplotype within an amplicon.
UNASSIGNED: We evaluate possible interpretations of these findings, and reviewed precedents for rapid selection of genomes with multiple mutations in RNA viruses. These considerations suggest that intra-host evolution may be sufficient to generate minority sequences which are closely related to sequences typical of other clades. The results provide a model for the origin of variants of concern during epidemic spread─in particular Omicron lineages─that does not require prolonged infection, involvement of immunocompromised individuals, or participation of intermediate, non-human hosts.
UNASSIGNED: Here we use high resolution ultra-deep sequencing to analyze SARS-CoV-2 mutant spectra.
UNASSIGNED: In 6 out of 11 SARS-CoV-2 isolates from COVID-19 patients, the mutant spectrum of the spike (S)-coding region included two or more amino acids or deletions, that correspond to discordant viral clades. A similar observation is reported for laboratory populations of SARS-CoV-2 USA-WA1/2020, following a cell culture infection in the presence of remdesivir, ribavirin or their combinations. Moreover, some of the clade-discordant genome residues are found in the same haplotype within an amplicon.
UNASSIGNED: We evaluate possible interpretations of these findings, and reviewed precedents for rapid selection of genomes with multiple mutations in RNA viruses. These considerations suggest that intra-host evolution may be sufficient to generate minority sequences which are closely related to sequences typical of other clades. The results provide a model for the origin of variants of concern during epidemic spread─in particular Omicron lineages─that does not require prolonged infection, involvement of immunocompromised individuals, or participation of intermediate, non-human hosts.
摘要：
■给定进化枝的SARS-CoV-2分离株可能含有低频率基因组,其编码不同进化枝典型的氨基酸或缺失。
■在这里，我们使用高分辨率超深度测序来分析SARS-CoV-2突变光谱。
■在来自COVID-19患者的11株SARS-CoV-2分离株中，有6株尖峰(S)编码区的突变谱包括两个或多个氨基酸或缺失，对应于不一致的病毒进化枝。据报道，在存在remdesivir的细胞培养物感染后，SARS-CoV-2USA-WA1/2020的实验室人群也有类似的观察结果，利巴韦林或其组合。此外，一些进化枝不一致的基因组残基在扩增子内的相同单倍型中发现。
■我们评估了对这些发现的可能解释，并回顾了快速选择RNA病毒中具有多个突变的基因组的先例。这些考虑表明，宿主内进化可能足以产生与其他进化枝典型序列密切相关的少数序列。这些结果为流行病传播过程中引起关注的变异的起源提供了一个模型-特别是Omicron谱系-不需要长时间感染，免疫受损个体的参与，或中间的参与，非人类宿主。
■在这里，我们使用高分辨率超深度测序来分析SARS-CoV-2突变光谱。
■在来自COVID-19患者的11株SARS-CoV-2分离株中，有6株尖峰(S)编码区的突变谱包括两个或多个氨基酸或缺失，对应于不一致的病毒进化枝。据报道，在存在remdesivir的细胞培养物感染后，SARS-CoV-2USA-WA1/2020的实验室人群也有类似的观察结果，利巴韦林或其组合。此外，一些进化枝不一致的基因组残基在扩增子内的相同单倍型中发现。
■我们评估了对这些发现的可能解释，并回顾了快速选择RNA病毒中具有多个突变的基因组的先例。这些考虑表明，宿主内进化可能足以产生与其他进化枝典型序列密切相关的少数序列。这些结果为流行病传播过程中引起关注的变异的起源提供了一个模型-特别是Omicron谱系-不需要长时间感染，免疫受损个体的参与，或中间的参与，非人类宿主。
