Cargando…

The genetic variability, phylogeny and functional significance of E6, E7 and LCR in human papillomavirus type 52 isolates in Sichuan, China

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Song, Zhilin, Cui, Yanru, Li, Qiufu, Deng, Junhang, Ding, Xianping, He, Jiaoyu, Liu, Yiran, Ju, Zhuang, Fang, Liyuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091156/
https://www.ncbi.nlm.nih.gov/pubmed/33941222
http://dx.doi.org/10.1186/s12985-021-01565-5
_version_ 1783687421475422208
author Song, Zhilin
Cui, Yanru
Li, Qiufu
Deng, Junhang
Ding, Xianping
He, Jiaoyu
Liu, Yiran
Ju, Zhuang
Fang, Liyuan
author_facet Song, Zhilin
Cui, Yanru
Li, Qiufu
Deng, Junhang
Ding, Xianping
He, Jiaoyu
Liu, Yiran
Ju, Zhuang
Fang, Liyuan
author_sort Song, Zhilin
collection PubMed
description 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 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 7387–7391 (TTATG) and 7698–7700 (CTT) in all samples. A deletion was found between the nucleotide sites 7287–7288 (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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12985-021-01565-5.
format Online
Article
Text
id pubmed-8091156
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-80911562021-05-03 The genetic variability, phylogeny and functional significance of E6, E7 and LCR in human papillomavirus type 52 isolates in Sichuan, China Song, Zhilin Cui, Yanru Li, Qiufu Deng, Junhang Ding, Xianping He, Jiaoyu Liu, Yiran Ju, Zhuang Fang, Liyuan Virol J Research 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 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 7387–7391 (TTATG) and 7698–7700 (CTT) in all samples. A deletion was found between the nucleotide sites 7287–7288 (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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12985-021-01565-5. BioMed Central 2021-05-03 /pmc/articles/PMC8091156/ /pubmed/33941222 http://dx.doi.org/10.1186/s12985-021-01565-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Song, Zhilin
Cui, Yanru
Li, Qiufu
Deng, Junhang
Ding, Xianping
He, Jiaoyu
Liu, Yiran
Ju, Zhuang
Fang, Liyuan
The genetic variability, phylogeny and functional significance of E6, E7 and LCR in human papillomavirus type 52 isolates in Sichuan, China
title The genetic variability, phylogeny and functional significance of E6, E7 and LCR in human papillomavirus type 52 isolates in Sichuan, China
title_full The genetic variability, phylogeny and functional significance of E6, E7 and LCR in human papillomavirus type 52 isolates in Sichuan, China
title_fullStr The genetic variability, phylogeny and functional significance of E6, E7 and LCR in human papillomavirus type 52 isolates in Sichuan, China
title_full_unstemmed The genetic variability, phylogeny and functional significance of E6, E7 and LCR in human papillomavirus type 52 isolates in Sichuan, China
title_short The genetic variability, phylogeny and functional significance of E6, E7 and LCR in human papillomavirus type 52 isolates in Sichuan, China
title_sort genetic variability, phylogeny and functional significance of e6, e7 and lcr in human papillomavirus type 52 isolates in sichuan, china
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091156/
https://www.ncbi.nlm.nih.gov/pubmed/33941222
http://dx.doi.org/10.1186/s12985-021-01565-5
work_keys_str_mv AT songzhilin thegeneticvariabilityphylogenyandfunctionalsignificanceofe6e7andlcrinhumanpapillomavirustype52isolatesinsichuanchina
AT cuiyanru thegeneticvariabilityphylogenyandfunctionalsignificanceofe6e7andlcrinhumanpapillomavirustype52isolatesinsichuanchina
AT liqiufu thegeneticvariabilityphylogenyandfunctionalsignificanceofe6e7andlcrinhumanpapillomavirustype52isolatesinsichuanchina
AT dengjunhang thegeneticvariabilityphylogenyandfunctionalsignificanceofe6e7andlcrinhumanpapillomavirustype52isolatesinsichuanchina
AT dingxianping thegeneticvariabilityphylogenyandfunctionalsignificanceofe6e7andlcrinhumanpapillomavirustype52isolatesinsichuanchina
AT hejiaoyu thegeneticvariabilityphylogenyandfunctionalsignificanceofe6e7andlcrinhumanpapillomavirustype52isolatesinsichuanchina
AT liuyiran thegeneticvariabilityphylogenyandfunctionalsignificanceofe6e7andlcrinhumanpapillomavirustype52isolatesinsichuanchina
AT juzhuang thegeneticvariabilityphylogenyandfunctionalsignificanceofe6e7andlcrinhumanpapillomavirustype52isolatesinsichuanchina
AT fangliyuan thegeneticvariabilityphylogenyandfunctionalsignificanceofe6e7andlcrinhumanpapillomavirustype52isolatesinsichuanchina
AT songzhilin geneticvariabilityphylogenyandfunctionalsignificanceofe6e7andlcrinhumanpapillomavirustype52isolatesinsichuanchina
AT cuiyanru geneticvariabilityphylogenyandfunctionalsignificanceofe6e7andlcrinhumanpapillomavirustype52isolatesinsichuanchina
AT liqiufu geneticvariabilityphylogenyandfunctionalsignificanceofe6e7andlcrinhumanpapillomavirustype52isolatesinsichuanchina
AT dengjunhang geneticvariabilityphylogenyandfunctionalsignificanceofe6e7andlcrinhumanpapillomavirustype52isolatesinsichuanchina
AT dingxianping geneticvariabilityphylogenyandfunctionalsignificanceofe6e7andlcrinhumanpapillomavirustype52isolatesinsichuanchina
AT hejiaoyu geneticvariabilityphylogenyandfunctionalsignificanceofe6e7andlcrinhumanpapillomavirustype52isolatesinsichuanchina
AT liuyiran geneticvariabilityphylogenyandfunctionalsignificanceofe6e7andlcrinhumanpapillomavirustype52isolatesinsichuanchina
AT juzhuang geneticvariabilityphylogenyandfunctionalsignificanceofe6e7andlcrinhumanpapillomavirustype52isolatesinsichuanchina
AT fangliyuan geneticvariabilityphylogenyandfunctionalsignificanceofe6e7andlcrinhumanpapillomavirustype52isolatesinsichuanchina