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L1 and L2 gene polymorphisms in HPV-58 and HPV-33: implications for vaccine design and diagnosis
BACKGROUND: Cervical cancer is associated with infection by certain subtypes of human papillomavirus (HPV). The L1 protein comprising HPV vaccine formulations elicits high-titre neutralizing antibodies and confers protection against specific HPV subtypes. HPV L2 protein is an attractive candidate fo...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5055703/ https://www.ncbi.nlm.nih.gov/pubmed/27717385 http://dx.doi.org/10.1186/s12985-016-0629-9 |
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author | Chen, Zuyi Jing, Yaling Wen, Qiang Ding, Xianping Zhang, Shun Wang, Tao Zhang, Yiwen Zhang, Jianhui |
author_facet | Chen, Zuyi Jing, Yaling Wen, Qiang Ding, Xianping Zhang, Shun Wang, Tao Zhang, Yiwen Zhang, Jianhui |
author_sort | Chen, Zuyi |
collection | PubMed |
description | BACKGROUND: Cervical cancer is associated with infection by certain subtypes of human papillomavirus (HPV). The L1 protein comprising HPV vaccine formulations elicits high-titre neutralizing antibodies and confers protection against specific HPV subtypes. HPV L2 protein is an attractive candidate for cross-protective vaccines. HPV-33 and HPV-58 are very prevalent among Chinese women. METHODS: To study the gene intratypic variations and polymorphisms of HPV-33 and HPV-58 L1/L2 in Sichuan China, HPV-33 and HPV-58 L1 and L2 genes were sequenced and compared with other genes submitted to GenBank. Phylogenetic trees were constructed by maximum-likelihood and the Kimura 2-parameters methods (MEGA 6). The secondary structure was analyzed by PSIPred software, and HPV-33 and HPV-58 L1 homology models were created by SWISS-MODEL software. The selection pressures acting on the L1/L2 genes were estimated by PAML 4.8. RESULTS: Among 124 HPV-33 L1 sequences 20 single nucleotide mutations were observed included 8/20 non-synonymous and 12/20 synonymous mutations. The 101 HPV-33 L2 sequences included 12 single nucleotide mutations comprising 7/12 non-synonymous and 5/12 synonymous mutations. The 223 HPV-58 L1 sequences included 32 single nucleotide mutations comprising 9/32 non-synonymous and 23/32 synonymous mutations. The 201 HPV-58 L2 sequences comprised 26 single nucleotide mutations including 9/26 non-synonymous and 17/26 synonymous mutations. Selective pressure analysis showed that most of the common non-synonymous mutations showed a positive selection. HPV-33 and HPV-58 L2 were more stable than HPV-33 and HPV-58 L1. CONCLUSIONS: HPV-33 and HPV-58 L2 were better candidates as clinical diagnostic targets compared with HPV-33 and HPV-58 L1. Clinical diagnostic probes and second-generation polyvalent vaccines should be designed on the basis of the unique sequence of HPV-33 and 58 L1/L2 variations in Sichuan, to improve the accuracy of clinical detection and the protective efficiency of vaccines. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0629-9) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5055703 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-50557032016-10-19 L1 and L2 gene polymorphisms in HPV-58 and HPV-33: implications for vaccine design and diagnosis Chen, Zuyi Jing, Yaling Wen, Qiang Ding, Xianping Zhang, Shun Wang, Tao Zhang, Yiwen Zhang, Jianhui Virol J Research BACKGROUND: Cervical cancer is associated with infection by certain subtypes of human papillomavirus (HPV). The L1 protein comprising HPV vaccine formulations elicits high-titre neutralizing antibodies and confers protection against specific HPV subtypes. HPV L2 protein is an attractive candidate for cross-protective vaccines. HPV-33 and HPV-58 are very prevalent among Chinese women. METHODS: To study the gene intratypic variations and polymorphisms of HPV-33 and HPV-58 L1/L2 in Sichuan China, HPV-33 and HPV-58 L1 and L2 genes were sequenced and compared with other genes submitted to GenBank. Phylogenetic trees were constructed by maximum-likelihood and the Kimura 2-parameters methods (MEGA 6). The secondary structure was analyzed by PSIPred software, and HPV-33 and HPV-58 L1 homology models were created by SWISS-MODEL software. The selection pressures acting on the L1/L2 genes were estimated by PAML 4.8. RESULTS: Among 124 HPV-33 L1 sequences 20 single nucleotide mutations were observed included 8/20 non-synonymous and 12/20 synonymous mutations. The 101 HPV-33 L2 sequences included 12 single nucleotide mutations comprising 7/12 non-synonymous and 5/12 synonymous mutations. The 223 HPV-58 L1 sequences included 32 single nucleotide mutations comprising 9/32 non-synonymous and 23/32 synonymous mutations. The 201 HPV-58 L2 sequences comprised 26 single nucleotide mutations including 9/26 non-synonymous and 17/26 synonymous mutations. Selective pressure analysis showed that most of the common non-synonymous mutations showed a positive selection. HPV-33 and HPV-58 L2 were more stable than HPV-33 and HPV-58 L1. CONCLUSIONS: HPV-33 and HPV-58 L2 were better candidates as clinical diagnostic targets compared with HPV-33 and HPV-58 L1. Clinical diagnostic probes and second-generation polyvalent vaccines should be designed on the basis of the unique sequence of HPV-33 and 58 L1/L2 variations in Sichuan, to improve the accuracy of clinical detection and the protective efficiency of vaccines. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0629-9) contains supplementary material, which is available to authorized users. BioMed Central 2016-10-07 /pmc/articles/PMC5055703/ /pubmed/27717385 http://dx.doi.org/10.1186/s12985-016-0629-9 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Chen, Zuyi Jing, Yaling Wen, Qiang Ding, Xianping Zhang, Shun Wang, Tao Zhang, Yiwen Zhang, Jianhui L1 and L2 gene polymorphisms in HPV-58 and HPV-33: implications for vaccine design and diagnosis |
title | L1 and L2 gene polymorphisms in HPV-58 and HPV-33: implications for vaccine design and diagnosis |
title_full | L1 and L2 gene polymorphisms in HPV-58 and HPV-33: implications for vaccine design and diagnosis |
title_fullStr | L1 and L2 gene polymorphisms in HPV-58 and HPV-33: implications for vaccine design and diagnosis |
title_full_unstemmed | L1 and L2 gene polymorphisms in HPV-58 and HPV-33: implications for vaccine design and diagnosis |
title_short | L1 and L2 gene polymorphisms in HPV-58 and HPV-33: implications for vaccine design and diagnosis |
title_sort | l1 and l2 gene polymorphisms in hpv-58 and hpv-33: implications for vaccine design and diagnosis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5055703/ https://www.ncbi.nlm.nih.gov/pubmed/27717385 http://dx.doi.org/10.1186/s12985-016-0629-9 |
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