Analysis of Emerging Variants in Structured Regions of the SARS-CoV-2 Genome.
Analysis of Emerging Variants in Structured Regions of the SARS-CoV-2 Genome.
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DOI：
10.1177/11769343211014167
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Massi F
中科院分区：
文献类型：
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作者：
Ryder SP;Morgan BR;Coskun P;Antkowiak K;Massi F
严重急性呼吸综合征冠状病毒2(SARS-CoV-2)大流行促使人们广泛努力了解其流行病学和致病机制。现代高通量测序技术已经导致大量SARS-CoV-2基因组序列存储在精选的储存库中，这对绘制病毒在全球的传播情况很有用。它们还提供了一个实时观察病毒演变的独特机会。在这里，我们评估了两组SARS-CoV-2基因组序列，以确定SARS-CoV-2基因组结构顺式调控元件中的新出现的变异。总体而言，有20个变异存在至少0.5%的次要等位基因频率。几个增强了茎环1在5ʹ非翻译区的稳定性，包括一组延长其长度的共生变体。一个似乎调节了ORF1a和ORF1b之间移帧假结的稳定性，另一个扰动了3ʹ非编码区中的双SS分子开关。最后，5个变异体破坏了3ʹ非编码区高变区内的结构元件的稳定性，包括S2M(茎环2 m)自私遗传元件，这引发了这些结构在病毒复制中的功能相关性的问题。其中两个最丰富的变异似乎是由RNA编辑引起的，这表明宿主-病毒防御有助于SARS-CoV-2基因组的异质性。我们的分析对以病毒顺式调控RNA结构或序列为靶点的治疗方法的发展具有重要意义。
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has motivated a widespread effort to understand its epidemiology and pathogenic mechanisms. Modern high-throughput sequencing technology has led to the deposition of vast numbers of SARS-CoV-2 genome sequences in curated repositories, which have been useful in mapping the spread of the virus around the globe. They also provide a unique opportunity to observe virus evolution in real time. Here, we evaluate two sets of SARS-CoV-2 genomic sequences to identify emerging variants within structured cis-regulatory elements of the SARS-CoV-2 genome. Overall, 20 variants are present at a minor allele frequency of at least 0.5%. Several enhance the stability of Stem Loop 1 in the 5ʹ untranslated region (UTR), including a group of co-occurring variants that extend its length. One appears to modulate the stability of the frameshifting pseudoknot between ORF1a and ORF1b, and another perturbs a bi-ss molecular switch in the 3ʹUTR. Finally, 5 variants destabilize structured elements within the 3ʹUTR hypervariable region, including the S2M (stem loop 2 m) selfish genetic element, raising questions as to the functional relevance of these structures in viral replication. Two of the most abundant variants appear to be caused by RNA editing, suggesting host-viral defense contributes to SARS-CoV-2 genome heterogeneity. Our analysis has implications for the development of therapeutics that target viral cis-regulatory RNA structures or sequences.