Phylogenetic Analyses of HPV53 and Prediction of B and T Cell Epitopes
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摘要: 目的 基于全长序列分析HPV53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、二级结构和B、T细胞抗原表位进行预测。 方法 从NCBI数据库获取HPV53全长序列并构建进化树。使用ProtParam分析蛋白理化性质;PSIPRED和SOPMA预测二级结构。利用ABCpred和IEDB分别预测B、T细胞抗原表位;并结合DNASTARProtean软件对肽段的柔韧性、亲水性、表面可及性、抗原性评分,以及Vaxijen评分等其他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13个其他高危型HPV的同源性进行分析。 结果 来自不同国家地区的48个HPV53分离株可被分为A、B、C三个主要进化分支。三个分支的代表株病毒的蛋白理化性质相似,二级结构存在部分小差异。B、T细胞抗原表位预测和筛选后,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。经同源性分析后发现,E4和E6区域的B细胞抗原表位TTPIRPPPPPRPWAPT和CYRCQHPLTPEEKQLH,以及L2区域的T细胞抗原表位SGVHSYEEIPMQ与HPV56具有较高的同源性(均>90%)。 结论 通过生物信息学方法分析和预测发现HPV53的病毒蛋白中含有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理论依据。Abstract: Objective The objective of this study was to construct phylogenetic trees based on HPV53 full length sequences, as well as to predict the physical and chemical parameters, secondary structure, B and T cell epitopes of HPV53 proteins (E1, E2, E4, E6, E7, L1, and L2). Method Full length of HPV53 variants were Obtained from the GenBank and a phylogenetic tree was constructed to define 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, hydrophilicity, surface accessibility, antigenicity of predicted B and T cell epitopes were further predicted by bioinformatic methods (e.g., DNASTAR-Protean, VaxiJen, etc.). 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 Phylogenetic analyses clustered HPV53 variants into 3 lineages designated A, B, and C. The physicochemical properties of three different HPV53 variants (representing A, B, and C lineages, respectively) were similar, while slight differences in secondary structure were observed. There were 6 potential dominant B cell epitopes and 9 potential dominant T cell epitopes were predicted for HPV53 proteins. Among these epitopes, B cell epitopes TTPIRPPPPPRPWAPT in E4 region and CYRCQHPLTPEEKQLH in E6 region, and T cell epitopes SGVHSYEEIPMQ in L2 region showed high homologous to HPV56 (all>90%). Conclusions Using bioinformatic tools, B and T cell epitopes for all proteins of HPV53 were predicted, which provides the basis for further research on epitope vaccines against HPV53.
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Key words:
- human papillomavirus type 53 /
- phylogenetic analyses /
- B cell /
- T cell /
- epitopes prediction
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