1.Genetic variation analyses of human papillomavirus 39 and prediction of T and B Cell epitopes
Yuxiao ZHANG ; Yijuan YANG ; Li WANG ; Sihan LAN ; Jing YU ; Jie HE ; Hongping ZHANG ; Min FENG
Chinese Journal of Experimental and Clinical Virology 2025;39(1):9-17
Objective:This 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).Methods:A 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.Results:HPV39 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.Conclusions:Bioinformatics 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 investigated, providing valuable theoretical support for the development of HPV39-related peptide-based vaccines and therapeutics.
2.Genetic variation analyses of human papillomavirus 39 and prediction of T and B Cell epitopes
Yuxiao ZHANG ; Yijuan YANG ; Li WANG ; Sihan LAN ; Jing YU ; Jie HE ; Hongping ZHANG ; Min FENG
Chinese Journal of Experimental and Clinical Virology 2025;39(1):9-17
Objective:This 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).Methods:A 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.Results:HPV39 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.Conclusions:Bioinformatics 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 investigated, providing valuable theoretical support for the development of HPV39-related peptide-based vaccines and therapeutics.
3.Phylogenetic Analyses of HPV53 and Prediction of B and T Cell Epitopes
Medical Journal of Peking Union Medical College Hospital 2024;15(6):1364-1371
To construct phylogenetic trees based on HPV53 full length sequences, and predict the physical and chemical parameters, secondary structure, B and T cell epitopes of HPV53 proteins(E1, E2, E4, E6, E7, L1, and L2). 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, hydrophilicity, surface accessibility, antigenicity of predicted B and T cell epitopes were further predicted by bioinformatic 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. 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 predominantly α-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%). Bioinformatics analysis and prediction revealed that HPV53 isolates could be clustered into three main evolutionary branches labeled as A, B, and C. These branches exhibited similar physicochemical properties, with minor differences in their secondary structure. Moreover, HPV53 viral proteins contained both B-cell and T-cell antigenic epitopes. These results lay the foundation for further research on vaccines and drugs based on HPV53-related peptides.
4.Phylogenetic Analyses of HPV53 and Prediction of B and T Cell Epitopes
Medical Journal of Peking Union Medical College Hospital 2024;15(6):1364-1371
To construct phylogenetic trees based on HPV53 full length sequences, and predict the physical and chemical parameters, secondary structure, B and T cell epitopes of HPV53 proteins(E1, E2, E4, E6, E7, L1, and L2). 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, hydrophilicity, surface accessibility, antigenicity of predicted B and T cell epitopes were further predicted by bioinformatic 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. 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 predominantly α-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%). Bioinformatics analysis and prediction revealed that HPV53 isolates could be clustered into three main evolutionary branches labeled as A, B, and C. These branches exhibited similar physicochemical properties, with minor differences in their secondary structure. Moreover, HPV53 viral proteins contained both B-cell and T-cell antigenic epitopes. These results lay the foundation for further research on vaccines and drugs based on HPV53-related peptides.
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