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严重急性呼吸综合征冠状病毒2(SARS-CoV-2)奥密克戎亚变体之间增强的重组有助于病毒免疫逃逸。

Enhanced recombination among Omicron subvariants of SARS-CoV-2 contributes to viral immune escape.

作者信息

Shiraz Rishad, Tripathi Shashank

机构信息

Microbiology and Cell Biology Department, Indian Institute of Science, Bengaluru, India.

Centre for Infectious Disease Research, Indian Institute of Science, Bengaluru, India.

出版信息

J Med Virol. 2023 Feb;95(2):e28519. doi: 10.1002/jmv.28519.

Abstract

Genetic recombination is an important driver of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution, which requires the coinfection of a single host cell with different SARS-CoV-2 strains. To understand the emergence and prevalence of recombinant SARS-CoV-2 lineages through time and space, we analyzed SARS-CoV-2 genome sequences collected from November 2019 to July 2022. We observed an extraordinary increase in the emergence of SARS-CoV-2 recombinant lineages during the Omicron wave, particularly in Northern America and Europe. This phenomenon was independent of the sequencing frequency or genetic diversity of circulating SARS-CoV-2 strains. The recombination breakpoints were more prevalent in the 3'-untranslated region of the viral genome. Importantly, we noted the enrichment of certain amino acids in the Spike protein of recombinant lineages, which have been reported to confer immune escape from neutralizing antibodies and increase angiotensin-converting enzyme 2 receptor binding in some cases. We also observed I42V amino acid change genetically fixated in the NSP14 of the Omicron lineage, which needs further characterization for its potential role in enhanced recombination. Overall, we report the important and timely observation of accelerated recombination in the currently circulating SARS-CoV-2 Omicron variants and explore their potential contribution to viral fitness, particularly immune escape.

摘要

基因重组是严重急性呼吸综合征冠状病毒2(SARS-CoV-2)进化的重要驱动力,这需要单个宿主细胞同时感染不同的SARS-CoV-2毒株。为了了解重组SARS-CoV-2谱系在时空上的出现和流行情况,我们分析了2019年11月至2022年7月收集的SARS-CoV-2基因组序列。我们观察到,在奥密克戎毒株流行期间,SARS-CoV-2重组谱系的出现显著增加,尤其是在北美和欧洲。这一现象与循环中的SARS-CoV-2毒株的测序频率或遗传多样性无关。重组断点在病毒基因组的3'非翻译区更为普遍。重要的是,我们注意到重组谱系的刺突蛋白中某些氨基酸的富集,据报道,这些氨基酸在某些情况下可赋予对中和抗体的免疫逃逸能力,并增加血管紧张素转换酶2受体的结合。我们还观察到奥密克戎谱系的NSP14中I42V氨基酸变化在基因上固定下来,其在增强重组中的潜在作用需要进一步表征。总体而言,我们报告了对当前流行的SARS-CoV-2奥密克戎变体中加速重组的重要且及时的观察结果,并探讨了它们对病毒适应性,特别是免疫逃逸的潜在贡献。

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