泉州市2022-2023年新冠病毒Omicron变异株基因组特征及S蛋白突变位点动态分析  

Dynamic Analysis on Spike Mutation and Genetic Characteristics of SARS⁃CoV⁃2 Omicron Strains in Quanzhou,China,from 2022 to 2023

作　　者：陈晓玲[1,3] 郑丹凤 龚彩婷 陈韵妍[1,3] 郑友限 林满芳[1,3] 陈霖霖 王伟明 CHEN Xiaoling;ZHENG Danfeng;GONG Caiting;CHEN Yunyan;ZHENG Youxian;LIN Manfang;CHEN Linlin;WANG Weiming(The Affiliated Quanzhou Center for Disease Control and Prevention of Fujian Medical University,Quanzhou 362000,China;School of Public Health,Fujian Medical University,Fuzhou 350122,China;Quanzhou Center for Disease Control and Prevention,Quanzhou 362000,China)

机构地区：[1]福建医科大学附属泉州市疾病预防控制中心,泉州362000 [2]福建医科大学公共卫生学院,福州350122 [3]泉州市疾病预防控制中心,泉州362000

出　　处：《病毒学报》2024年第1期97-105,共9页Chinese Journal of Virology

基　　金：泉州市科技计划项目(项目号:2020N068s),题目:基于病毒宏基因组学技术分析2019-nCoV感染者呼吸道的病毒谱特点及毒株分子流行病学特征。

摘　　要：本研究旨在了解泉州市新型冠状病毒(Severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)流行株的基因型别分布及全基因组特征,动态研究S蛋白关键结构域的突变规律。采用纳米孔测序获取2022年3月至2023年6月泉州市新冠病毒监测病例毒株的全基因组序列,对数据过滤后的641条优质序列进行基因型别鉴定、序列比对及突变位点统计,通过聚类热图动态分析S蛋白关键结构域的氨基酸突变规律,借助VarEPS系统完成变异对病毒传播和适应性影响评估。监测期间泉州地区流行株均为Omicron变异株,总体呈BA.2-BA.5-XBB谱系顺序更替,与同期全国流行趋势基本一致;核苷酸与氨基酸突变位点数分别为81个(79~84个)、57个(55~62个)且逐步增加;S蛋白RBM区有氨基酸变异更替现象,如G446V到G446S、T478K到T478R/N、F486I/V到F486S/P;近期在非BA.2.75流行期间频繁检出BA.2.75于NTD区的高频突变位点,如W152R、F157L、I210V且有上升趋势;不同时期在Furin裂解点或S2亚基区可检出不同的氨基酸突变,与同期流行株基因型别更替相关。这些氨基酸突变均可一定程度上降低S蛋白与中和抗体的稳定性,但对其与ACE2的结合状态改变不大,多为中性突变。从基因层面开展新冠病毒变异动态监测,可以帮助我们掌握区域基因型别特征及病毒变异进化规律,探索变异对病毒传播和适应性影响,及时预警关键变异。To understand the genotype distribution and genetic characteristics of SARS‐CoV‐2 in Quanzhou,China,and to dynamic surveillance the mutation on key domain of spike protein.The whole genome sequence of SARS‐CoV‐2 from surveillance cases in Quanzhou,China from 2022 to 2023 were detected by nanopore sequencing.A total of 641 sequences post quality control were genotyped,alignmented and dynamic analysed on the key mutation of spike protein by cluster heatmap.The influence of mutations on viral transmission and adaptability was evaluated by VarEPS.All the 641 cases were Omicron variants of SARS‐CoV‐2 shown as turnover of BA.2‐BA.5‐XBB lineage,in according with the national epidemic trend during the corresponding period.The numbers of mutations in nucleotides and amino acids were 81(79~84)and 57(55~62)with gradual growth.Turnovers of various amino acid substitutions were shown in Receptor binding motif region of spike protein,such as G446V to G446S,T478K to T478R/N and F486I/V to F486S/P.High‐frequency amino acid substitutions in N‐terminal domain region of BA.2.75 were detected during the non‐BA.2.75 epidemic,such as W152R,F157L and I210V.Various amino acid substitutions in the region of the Furin cleavage site and the S2 subunit were detected in various periods,associated with genotypic turnover.The stability of S protein binding to neutralizing antibodies was reduced accompanying all of these amino acid mutations,while hardly reduced binding to ACE2,and they were mostly neutral mutations.The dynamic surveillance on mutations of SARS‐CoV‐2 by genetic level can show the genotype characteristics and the evolution of virus,help to explore the effects of variation on viral transmission and adaptation,and give warning on the key mutations in time.

关 键 词：新型冠状病毒 奥密克戎 S蛋白 氨基酸突变 聚类热图 

分 类 号：R373.1[医药卫生—病原生物学]