人乳头瘤病毒39型遗传变异分析及T细胞与B细胞抗原表位预测  

Genetic variation analyses of human papillomavirus 39 and prediction of T and B Cell epitopes

作　　者：张誉小 杨一娟 王丽[1] 蓝锶菡 俞晶 何洁 张红平 冯敏[1] Zhang Yuxiao;Yang Yijuan;Wang Li;Lan Sihan;Yu Jing;He Jie;Zhang Hongping;Feng Min(Institute of Medical Biology,Chinese Academy of Medical Sciences&Peking Union Medical College,Kunming 650118,China;Peking University Cancer Hospital Yunnan,Yunnan Cancer Hospital,The Third Affiliated Hospital of Kunming Medical University,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 [2]北京大学肿瘤医院云南医院云南省肿瘤医院昆明医科大学第三附属医院妇科,昆明650118

出　　处：《中华实验和临床病毒学杂志》2025年第1期9-17,共9页Chinese Journal of Experimental and Clinical Virology

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);云南省兴滇英才支持计划-名医项目(XDYC-MY-2022-0056);云南省创新团队(202305AS00020)。

摘　　要：目的分析人乳头瘤病毒(Human papillomavirus,HPV)39基因组遗传变异特征,并对病毒早期蛋白(E1、E2、E6、E7)和晚期蛋白(L1、L2)的T、B细胞优势抗原表位进行预测和筛选。方法从临床样本和NCBI数据库中共获取70条HPV39全长序列构建进化树、分析基因多态性,并对病毒蛋白理化性质进行预测;采用IEDB和ABCpred预测T、B细胞抗原表位,并结合表位所在区域的二级结构,以及肽段的柔韧性、亲水性、表面可及性、抗原性评分等参数进一步筛选潜在优势抗原表位;最后对潜在优势抗原表位与12种高危型HPV进行同源性分析。结果HPV39突变株可分为两个进化分支,分布于不同进化分支的毒株具有其特定的突变模式。在不同病毒基因中,E7突变率最高,而E1突变率最低,但这些碱基/氨基酸突变未对病毒的理化性质产生明显影响。经预测和筛选后,L1、L2各获得5、6条B细胞潜在优势抗原表位;E1、E2、E6、E7分别获得18、10、4及1条HLA-I类T细胞潜在优势抗原表位;E1、E2、E6获得7、3及2条HLA-II类T细胞潜在优势抗原表位。同源性分析发现E1、E2、E6区域的T细胞抗原表位,以及L2中的B细胞抗原表位与HPV68、HPV33、HPV45和HPV59具有较高的同源性(93%~100%)。结论HPV39突变株可分为A、B两个主要进化分支,各进化分支具有其特定突变模式。病毒蛋白中含有可供进一步研究的T、B细胞潜在优势抗原表位,为HPV39相关多肽形式的疫苗和药物开发提供了更多理论依据。ObjectiveThis study aimed to analyze the genetic variation of the human papillomavirus(HPV)type 39 genomes and to predict and screen the dominant T-cell and B-cell epitopes of the viral early proteins(E1,E2,E6,E7)and late proteins(L1,L2).MethodsA total of 70 full-length sequences of HPV39 variants were retrieved from the clinical samples and the National Center for Biotechnology Information(NCBI)to construct a phylogenetic tree,analyze genetic polymorphisms,and predict the physicochemical properties of the viral proteins.Next,T-cell and B-cell epitopes were predicted using IEDB and ABCpred,and potential dominant epitopes were further selected based on parameters such as the secondary structure of the epitope region,peptide flexibility,hydrophilicity,surface accessibility and antigenicity.Finally,a homology analysis of the potential dominant epitopes was performed with 12 high-risk HPV types.ResultsHPV39 variants from different sources can be clustered into two lineages(A and B),each exhibiting distinct mutation patterns.The mutation rate was the highest in E7 and the lowest in E1 among the different viral genes.However,these nucleotide/amino acid mutations did not significantly impact the physicochemical properties of the viral proteins.After prediction and screening,5 and 6 potential dominant B-cell epitopes were identified in both L1 and L2,respectively.E1,E2,E6,and E7 yielded 18,10,4,and 1 potential dominant HLA-I restricted T-cell epitopes,respectively.Additionally,E1,E2,and E6 yielded 7,3,and 2 potential dominant HLA-II restricted T-cell epitopes,respectively.Homology analysis indicated that T-cell dominant epitopes in E1,E2,and E6,as well as B-cell epitopes in L2,showed high homology(93%-100%)with HPV68,HPV33,HPV45,and HPV59.ConclusionsBioinformatics analysis and prediction revealed that HPV39 variants can be clustered into two main evolutionary branches,A and B,each exhibiting a specific mutation pattern.The viral proteins contain potential dominant T-cell and B-cell epitopes that can be further investigat

关 键 词：人乳头瘤病毒39型 遗传变异分析 T细胞 B细胞 抗原表位预测 

分 类 号：R73[医药卫生—肿瘤]