HPV53进化关系分析及B细胞与T细胞抗原表位预测  

Phylogenetic Analyses of HPV53 and Prediction of B and T Cell Epitopes

作　　者：蓝锶菡 冯敏[1] LAN Sihan;FENG Min(Institute of Medical Biology,Chinese Academy of Medical Sciences&Peking Union Medical College,Kunming 650118,China)

机构地区：[1]中国医学科学院北京协和医学院医学生物学研究所,昆明650118

出　　处：《协和医学杂志》2024年第6期1364-1371,共8页Medical Journal of Peking Union Medical College Hospital

基　　金：中国医学科学院医学与健康科技创新工程⁃重大协同创新项目(2021⁃I2M⁃1⁃004);云南省卫生健康委员会医学学科带头人培养计划(D⁃2019023)。

摘　　要：目的基于全长序列分析人乳头瘤病毒(human papillomavirus,HPV)53不同分离株的进化关系,并对代表性分离株病毒蛋白(E1、E2、E4、E6、E7、L1和L2)的理化性质、二级结构及B细胞与T细胞抗原表位进行预测。方法检索美国国立生物技术信息中心(National Center for Biotechnology Information,NCBI)数据库,获取HPV53全长序列并构建进化树。采用ProtParam软件分析蛋白的理化性质,PSIPRED和SOPMA软件预测其二级结构。采用ABCpred和IEDB软件预测B、T细胞抗原表位,并结合肽段柔韧性、亲水性、表面可及性、抗原性及Vaxijen评分等参数进一步筛选潜在的优势抗原表位;最后对潜在优势抗原表位与13个高危型HPV进行同源性分析。结果检索NCBI数据库共下载54条HPV53全长序列,经去重后保留48条,来自不同国家/地区的HPV53分离株可划分为A、B、C三个主要进化分支。三个分支代表株病毒的蛋白理化性质相似,E1、E6和E7蛋白的二级结构以α螺旋为主,E2、E4、L1和L2以无规则卷曲为主。经预测和筛选后,共得到6个B细胞潜在优势抗原表位和9个T细胞潜在优势抗原表位,同源性分析发现,E4和E6区域的B细胞抗原表位TTPIRPPPPPRPWAPT和CYRCQHPLTPEEKQLH,及L2区域的T细胞抗原表位SGVHSYEEIPMQ与HPV56具有较高同源性(均>90%)。结论通过生物信息学方法分析和预测发现HPV53分离株可分为A、B、C三个主要进化分支,其理化性质相似,二级结构存在部分小差异,且病毒蛋白中含有B、T细胞抗原表位,为HPV53相关多肽形式的疫苗和抗体药物开发提供了更多理论依据。Objective To construct phylogenetic trees based on HPV53 full length sequences,and pre⁃dict the physical and chemical parameters,secondary structure,B and T cell epitopes of HPV53 proteins(E1,E2,E4,E6,E7,L1,and L2).Methods The full⁃length sequences of HPV53 variants were retrieved from the National Center for Biotechnology Information(NCBI),and a phylogenetic tree was constructed to delineate variant lineages.The physical and chemical parameters of HPV53 proteins were analyzed by ProtParam.The secondary structure of proteins was analyzed using PSIPRED and SOPMA.The B and T cell epitopes for HPV53 proteins were predicted by the IEDB analysis server and the ABCpred server,respectively.Then,to select the potential dominant B and T cell epitopes,more parameters including flexibility,hydrophi⁃licity,surface accessibility,antigenicity of predicted B and T cell epitopes were further predicted by bioinfor⁃matic methods such as VaxiJen.Finally,for homology analysis,the potential dominant B and T cell epitopes were compared with the 13 high⁃risk HPV subtypes using NCBI BLAST tool.Results A total of 54 full⁃length HPV53 sequences were retrieved from the NCBI database,with 48 entries remaining after deduplication.These 48 HPV53 isolates from different countries/regions were clustered into three main evolutionary branches labeled as lineages A,B,and C.The physicochemical properties of three different HPV53 variants(representing A,B,and C lineages,respectively)were similar.The secondary structure of the E1,E6,and E7 proteins was predominantlyα⁃helices,while E2,E4,L1,and L2 predominantly exhibited random coils.After prediction and screening,a total of 6 potential B⁃cell epitopes and 9 potential T⁃cell epitopes were identified on HPV53 proteins.Among these epitopes,B cell epitopes TTPIRPPPPPRPWAPT in E4 region,CYRCQHPLTPEEKQLH in E6 region,and T cell epitopes SGVHSYEEIPMQ in L2 region showed high homologous to HPV56(all>90%).Conclusions Bioinformatics analysis and prediction revealed that HPV53 isolates could

关 键 词：人乳头瘤病毒53型 进化分析 B细胞 T细胞 抗原表位预测 

分 类 号：R373[医药卫生—病原生物学] R737[医药卫生—基础医学]