新型冠状病毒刺突蛋白基因型分型与抗原性聚类的关系分析  

Analysis of the relationship between genotype clustering and antigenicity clustering of SARS-CoV-2 spike

作　　者：田欣心 张璐 汪萱怡 裘天颐 邱景璇 Tian Xinxin;Zhang Lu;Wang Xuanyi;Qiu Tianyi;Qiu Jingxuan(School of Health Science and Engineering,University of Shanghai for Science and Technology,Shanghai 200093,China;School of Life Sciences and Technology,Tongji University,Shanghai 200092,China;Institutes of Biomedical Sciences,Fudan University,Shanghai 200032,China;Biomedical Research Center,Zhongshan Hospital,Fudan University,Shanghai 200032,China)

机构地区：[1]上海理工大学健康科学与工程学院,上海200093 [2]同济大学生命科学与技术学院,上海200092 [3]复旦大学生物医学研究院,上海200032 [4]复旦大学附属中山医院实验研究中心,上海200032

出　　处：《国际生物制品学杂志》2023年第5期241-246,共6页International Journal of Biologicals

基　　金：国家自然科学基金(32000470,31900483)。

摘　　要：目的对新型冠状病毒刺突蛋白(spike,S)进行抗原性聚类与基因型聚簇的关联分析,为疫苗设计的方向提供参考。方法基于476条新型冠状病毒基因,分析S序列的氨基酸进化情况并构建系统发育树。在抗原抗体结合界面提取抗原表位并对序列进行三维空间结构模拟,将提取表位与模拟结构两两配对计算抗原性距离,构建抗原相似性聚类树。通过比较毒株对应的序列系统发育树和抗原相似性聚类树,评估新型冠状病毒进化与抗原性的关系。结果新型冠状病毒的系统发育树上不同谱系的毒株分别聚在相应的分支上,其中Alpha分支与Gamma分支相距最远,序列相似度最低;同时Omicron株的BA.1到BA.5分支聚在一起,呈现出高度的序列相似性,且与野生型毒株的距离较远。抗原性的聚类表明,Omicron株的5个谱系的抗原性聚集情况与序列聚类情况不一致,并未呈现出较为明显的抗原性聚类。结论新型冠状病毒S的抗原性聚类与序列聚类情况可能并不一致,而是更倾向于抗原表位的差异。疫苗设计中,考虑抗原性位点差异特征的设计思路将会比基于家族谱系的设计思路更为有效。Objective To analyze the association of antigenicity cluster and genotype cluster of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S),to provide reference for vaccine design.Methods Based on 476 SARS-CoV-2 gene sequences,the evolution of S was analyzed and the phylogenetic tree was constructed.Secondly,the antigen epitopes were extracted from the antigen-antibody binding interface and the 3D spatial structure of the sequences was simulated.The antigenicity distance was calculated by pairing the epitopes with the modeled structure,and the antigen similarity cluster tree was constructed.Finally,the relationship between evolution and antigenicity of SARS-CoV-2 was evaluated by comparing the sequence phylogenetic tree and the antigen similarity cluster tree corresponding to the virus strains.Results The phylogenetic tree was evenly distributed,and the strains of the same branch clustered together.The Alpha branch and the Gamma branch were the most distant and the least similar.BA.1-BA.5 lineages of Omicron clade were clustered together with high similarity.The antigenicity clustering was different from the phylogenetic tree for 5 Omicron lineages,which indicated the antigenicity cluster was not apparent.Conclusion The antigenic similarity of S is different from the sequence similarity,and rather rely on the difference between mutant epitopes,which indicated that for vaccine design,difference between antigenic sites is more reliable than the design based on different lineage.

关 键 词：新型冠状病毒 刺突蛋白 抗原表位 抗原性位点 系统发育树 

分 类 号：Q71[生物学—分子生物学] R373.9[医药卫生—病原生物学]