ABSTRACT The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus that is continuously evolving. Although its RNA-dependent RNA polymerase exhibits some exonuclease proofreading activity, viral sequence diversity can be produced by replication errors and host factors. A diversity of genetic variants can be observed in the intrahost viral population structure of infected individuals. Most mutations will follow a neutral molecular evolution and will not make significant contributions to variations within and between infected hosts. Herein, we profiled the intrasample genetic diversity of SARS-CoV-2 variants, also known as quasispecies, using high-throughput sequencing data sets from 15,289 infected individuals and infected cell lines. Despite high mutational background, we identified recurrent intragenetic variable positions in the samples analyzed, including several positions at the end of the gene encoding the viral spike (S) protein. Strikingly, we observed a high frequency of C→A missense mutations resulting in the S protein lacking the last 20 amino acids (SΔ20). We found that this truncated S protein undergoes increased processing and increased syncytium formation, presumably due to escaping M protein retention in intracellular compartments. Our findings suggest the emergence of a high-frequency viral sublineage that is not horizontally transmitted but potentially involved in intrahost disease cytopathic effects.
【저자키워드】 COVID-19, SARS-CoV-2, Spike protein, Syncytia, High-throughput sequencing, genetic variants, 【초록키워드】 Evolution, coronavirus, Mutation, S protein, Variation, Quasispecies, severe acute respiratory syndrome Coronavirus, virus, molecular evolution, M protein, Replication, Protein, Viral, SARS-CoV-2 variants, amino acids, Factors, Missense mutation, RNA-dependent RNA polymerase, genetic diversity, genetic variants, Genetic variant, variations, molecular, respiratory, disease, Amino acid, exonuclease, Frequency, Proofreading, Diversity, Neutral, data sets, acute respiratory syndrome, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, infected individual, infected individuals, sequence, hosts, sequencing data, viral spike, cytopathic effects, infected cell, gene encoding, MOST, syncytium formation, Host, produced, resulting, analyzed, involved, transmitted, the S protein, exhibit, 【제목키워드】 spike, identification, enhanced, Effect,