Identification of variants and therapeutic epitopes in HPV-33/HPV-58 E6 and E7 in Southwest China

He, Jiaoyu; Yang, Yasi; Chen, Zuyi; Liu, Yang; Bao, Shanfei; Zhao, Yun; Ding, Xianping

doi:10.1186/s12985-019-1168-y

Cited by 21 publications

(29 citation statements)

References 31 publications

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“…The retrieved sequences were searched against the SMART 4 ( Letunic and Bork, 2018 ) and the National Center for Biotechnology Information (NCBI) Conserved Domain Search Service tool 5 ( Lu et al, 2020 ) to confirm the conserved domains for the GH18 gene family. The number of amino acids, theoretical molecular weight (MW), and isoelectric point (PI) of the GH18 proteins were predicted using ProtParam 6 ( He et al, 2019 ). The subcellular localization was predicted using BUSCA 7 ( Savojardo et al, 2018 ) web server.…”

Section: Methodsmentioning

confidence: 99%

Genome-Wide Identification and Analysis of Chitinase GH18 Gene Family in Mycogone perniciosa

Yang

Sossah²,

Li³

et al. 2021

Front. Microbiol.

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Mycogone perniciosa causes wet bubble disease in Agaricus bisporus and various Agaricomycetes species. In a previous work, we identified 41 GH18 chitinase genes and other pathogenicity-related genes in the genome of M. perniciosa Hp10. Chitinases are enzymes that degrade chitin, and they have diverse functions in nutrition, morphogenesis, and pathogenesis. However, these important genes in M. perniciosa have not been fully characterized, and their functions remain unclear. Here, we performed a genome-wide analysis of M. perniciosa GH18 genes and analyzed the transcriptome profiles and GH18 expression patterns in M. perniciosa during the time course of infection in A. bisporus. Phylogenetic analysis of the 41 GH18 genes with those of 15 other species showed that the genes were clustered into three groups and eight subgroups based on their conserved domains. The GH18 genes clustered in the same group shared different gene structures but had the same protein motifs. All GH18 genes were localized in different organelles, were unevenly distributed on 11 contigs, and had orthologs in the other 13 species. Twelve duplication events were identified, and these had undergone both positive and purifying selection. The transcriptome analyses revealed that numerous genes, including transporters, cell wall degrading enzymes (CWDEs), cytochrome P450, pathogenicity-related genes, secondary metabolites, and transcription factors, were significantly upregulated at different stages of M. perniciosa Hp10 infection of A. bisporus. Twenty-three out of the 41 GH18 genes were differentially expressed. The expression patterns of the 23 GH18 genes were different and were significantly expressed from 3 days post-inoculation of M. perniciosa Hp10 in A. bisporus. Five differentially expressed GH18 genes were selected for RT-PCR and gene cloning to verify RNA-seq data accuracy. The results showed that those genes were successively expressed in different infection stages, consistent with the previous sequencing results. Our study provides a comprehensive analysis of pathogenicity-related and GH18 chitinase genes’ influence on M. perniciosa mycoparasitism of A. bisporus. Our findings may serve as a basis for further studies of M. perniciosa mycoparasitism, and the results have potential value for improving resistance in A. bisporus and developing efficient disease-management strategies to mitigate wet bubble disease.

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Section: Methodsmentioning

confidence: 99%

Genome-Wide Identification and Analysis of Chitinase GH18 Gene Family in Mycogone perniciosa

Yang

Sossah²,

Li³

et al. 2021

Front. Microbiol.

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“…The Immune Epitope Database (IEDB) server (http://www.iedb.org/) was used to predict the major HLA-I and HLA-II binding peptides [28,29]. In our study, we used IEDB recommended methods to predict the epitopes against 34 HLA-I alleles by comprehensive analysis the frequency of Chinese in allele frequency net database(AFND) (http://www.allelefrequencies.net/hla6006a.asp) and 27 HLA-II allele [30].…”

Section: T and B Cell Antigen Epitope Predictionmentioning

confidence: 99%

“…According to the IEDB recommended method, among HLA-I a low percentile rank (PR) showed a good binder, among HLA-II a low adjusted rank (AR) showed a good binder. In prediction of HLA-I and HLA-II restricted epitopes the PR≤1.0 and AR≤5.0 were selected for the further analysis, respectively [29,31].…”

Section: T and B Cell Antigen Epitope Predictionmentioning

confidence: 99%

“…The ABCpred server (https://webs.iiitd.edu.in/raghava/abcpred/index.html) was used to predict B cell antigen epitopes of HPV-52 E6/E7 reference and variant sequences according to the default parameters [32]. The higher predicted score represented a better affinity [29,31]. The server is able to predict epitopes with 65.93% accuracy using recurrent neural network.…”

Section: T and B Cell Antigen Epitope Predictionmentioning

confidence: 99%

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The Genetic Variability, Phylogeny and Functional Significance of E6, E7 and LCR in Human Papillomavirus type 52 Isolates in Sichuan, China

Song

Deng

et al. 2020

Preprint

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Background: Variations in human papillomavirus (HPV) E6 and E7 have been shown to be closely related to the persistence of the virus and the occurrence and development of cervical cancer. Long control region (LCR) of HPV has been shown multiple functions on regulating viral transcription. In recent years, there have been reports on E6/E7/LCR of HPV-16 and HPV-58, but there are few studies on HPV-52, especially for LCR. In this study, we focused on gene polymorphism of the HPV-52 E6/E7/LCR sequences, assessed the effects of variations on the immune recognition of viral E6 and E7 antigens, predicted the effect of LCR variations on transcription factor binding sites and provided more basic date for further study of E6/E7/LCR in Chengdu, China. Methods: LCR/E6/E7 of the HPV-52 were amplified and sequenced to do polymorphic and phylogenetic analysis. Sequences were aligned with the reference sequence by MEGA 7.0 to identify SNP. A neighbor-joining phylogenetic tree was constructed by MEGA 7.0, followed by the secondary structure prediction of the related proteins using PSIPRED 4.0. The selection pressure of E6 and E7 coding regions were estimated by Bayes empirical Bayes analysis of PAML 4.9. The HLA class-I and II binding peptides were predicted by the Immune Epitope Database (IEDB) server. The B cell epitopes were predicted by ABCpred server. Transcription factor binding sites in LCR were predicted by JASPAR database. Results: 50 SNP sites (6 in E6, 10 in E7, 34 in LCR) were found. From the most variable to the least variable, the nucleotide variations were LCR>E7> E6. Two deletions were found between the nucleotide sites 7387 to 7391 (TTATG) and 7698 to 7700 (CTT) in all samples. A deletion was found between the nucleotide sites 7287 to 7288 (TG) in 97.56% (40/41) of the samples. The combinations of all the SNP sites and deletions resulted in 12 unique sequences. As shown in the neighbor-joining phylogenetic tree, except for one belonging to sub-lineage C2, others sequences clustered into sub-lineage B2. No positive selection was observed in E6 and E7. 8 non-synonymous amino acid substitutions (including E3Q and K93R in the E6, and T37I, S52D, Y59D, H61Y, D64N and L99R in the E7) were potential affecting multiple putative epitopes for both CD4+ and CD8+ T-cells and B-cells. A7168G was the most variable site (100%) and the binding sites for transcription factor VAX1 in LCR. In addition, the prediction results showed that LCR had the high probability binding sites for transcription factors SOX9, FOS, RAX, HOXA5, VAX1 and SRY. Conclusion: This study provides basic data for understanding the relation among E6/E7/LCR mutations, lineages and carcinogenesis. Furthermore, it provides an insight into the intrinsic geographical relatedness and biological differences of the HPV-52 variants, and contributes to further research on the HPV-52 therapeutic vaccine development.

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“…B cells play an important role in the immunotherapy of HPV-related tumors and in response to cervical epithelial tumors and cervical cancers caused by HPV. 18 The B-cell epitope prediction of E6 and E7 genes are of great significance in vaccine design and disease diagnosis. 19 Therefore, E6 and E7 oncoproteins are generally considered to be ideal targets for anti-HPV therapeutic vaccines.…”

Section: Introductionmentioning

confidence: 99%

Genetic variation of E6 and E7 genes of human papillomavirus 52 from Central China

Yong-lin

et al. 2020

Journal of Medical Virology

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Cervical cancer is the fourth most common malignant tumor in women worldwide and is closely related to human papillomavirus (HPV). Women have the highest susceptibility to HPV‐52 type in Jingzhou, China. In this study, E6‐E7 sequences of 183 HPV‐52 positive samples were amplified by a polymerase chain reaction and sequenced. HPV‐52 E6‐E7 gene variations were analyzed. The phylogenetic tree was constructed using the Kimura 2‐parameter method. The secondary structure of the protein was analyzed. The selective pressure to E6‐E7 genes was estimated using PAML. In addition, the B cell epitopes of the E6‐E7 sequences in HPV‐52 were predicted by the ABCpred server. In E6 sequences, 15 single nucleotide variants were observed, including 6 nonsynonymous variants and 9 synonymous variants. In E7 sequences, 19 single nucleotide variants occurred, including 10 nonsynonymous variants and 9 synonymous variants. Six amino acid variants, including 3 nonconservative substitutions, were found in sequences encoding the alpha helix. Eight amino acid variants, including three nonconservative substitutions, occurred in sequences encoding the strand. Through phylogenetic analysis, the E6‐E7 sequences were mainly distributed in B lineage. In HPV‐52 E6‐E7 sequences, no positively selected site was found. The nonconservative substitutions, such as K93R, K93E in E6, T37I, and D38N in E7, affected multiple hypothetical epitopes in the B cell. This study provides information for the investigation of HPV epidemic characters. The discovery of new variants of HPV‐52 may lay the basis for the development of the virus diagnosis, further study of cervical cancer, and vaccine design in Central China.

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Identification of variants and therapeutic epitopes in HPV-33/HPV-58 E6 and E7 in Southwest China

Cited by 21 publications

References 31 publications

Genome-Wide Identification and Analysis of Chitinase GH18 Gene Family in Mycogone perniciosa

Genome-Wide Identification and Analysis of Chitinase GH18 Gene Family in Mycogone perniciosa

The Genetic Variability, Phylogeny and Functional Significance of E6, E7 and LCR in Human Papillomavirus type 52 Isolates in Sichuan, China

Genetic variation of E6 and E7 genes of human papillomavirus 52 from Central China

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