Whole-genome analysis of human papillomavirus genotypes 52 and 58 isolated from Japanese women with cervical intraepithelial neoplasia and invasive cervical cancer
Abstract Background Human papillomavirus genotypes 52 and 58 (HPV52/58) are frequently detected in patients with cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC) in East Asian countries including Japan. As with other HPV genotypes, HPV52/58 consist of multiple lineages of...
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doaj-50904b1b6c2d49509c179ed320f677c92020-11-24T21:38:49ZengBMCInfectious Agents and Cancer1750-93782017-08-0112111210.1186/s13027-017-0155-4Whole-genome analysis of human papillomavirus genotypes 52 and 58 isolated from Japanese women with cervical intraepithelial neoplasia and invasive cervical cancerYuri Tenjimbayashi0Mamiko Onuki1Yusuke Hirose2Seiichiro Mori3Yoshiyuki Ishii4Takamasa Takeuchi5Nobutaka Tasaka6Toyomi Satoh7Tohru Morisada8Takashi Iwata9Shingo Miyamoto10Koji Matsumoto11Akihiko Sekizawa12Iwao Kukimoto13Department of Obstetrics and Gynecology, Showa University School of MedicineDepartment of Obstetrics and Gynecology, Showa University School of MedicineDepartment of Obstetrics and Gynecology, Showa University School of MedicinePathogen Genomics Center, National Institute of Infectious DiseasesPathogen Genomics Center, National Institute of Infectious DiseasesPathogen Genomics Center, National Institute of Infectious DiseasesDepartment of Obstetrics and Gynecology, Faculty of Medicine, University of TsukubaDepartment of Obstetrics and Gynecology, Faculty of Medicine, University of TsukubaDepartment of Obstetrics and Gynecology, Keio University School of MedicineDepartment of Obstetrics and Gynecology, Keio University School of MedicineDepartment of Obstetrics and Gynecology, Showa University School of MedicineDepartment of Obstetrics and Gynecology, Showa University School of MedicineDepartment of Obstetrics and Gynecology, Showa University School of MedicinePathogen Genomics Center, National Institute of Infectious DiseasesAbstract Background Human papillomavirus genotypes 52 and 58 (HPV52/58) are frequently detected in patients with cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC) in East Asian countries including Japan. As with other HPV genotypes, HPV52/58 consist of multiple lineages of genetic variants harboring less than 10% differences between complete genome sequences of the same HPV genotype. However, site variations of nucleotide and amino acid sequences across the viral whole-genome have not been fully examined for HPV52/58. The aim of this study was to investigate genetic variations of HPV52/58 prevalent among Japanese women by analyzing the viral whole-genome sequences. Methods The entire genomic region of HPV52/58 was amplified by long-range PCR with total cellular DNA extracted from cervical exfoliated cells isolated from Japanese patients with CIN or ICC. The amplified DNA was subjected to next generation sequencing to determine the complete viral genome sequences. Phylogenetic analyses were performed with the whole-genome sequences to assign variant lineages/sublineages to the HPV52/58 isolates. The variability in amino acid sequences of viral proteins was assessed by calculating the Shannon entropy scores at individual amino acid positions of HPV proteins. Results Among 52 isolates of HPV52 (CIN1, n = 20; CIN2/3, n = 21; ICC, n = 11), 50 isolates belonged to lineage B (sublineage B2) and two isolates belonged to lineage A (sublineage A1). Among 48 isolates of HPV58 (CIN1, n = 21; CIN2/3, n = 19; ICC, n = 8), 47 isolates belonged to lineage A (sublineages A1/A2/A3) and one isolate belonged to lineage C. Single nucleotide polymorphisms specific for individual variant lineages were determined throughout the viral genome based on multiple sequence alignments of the Japanese HPV52/58 isolates and reference HPV52/58 genomes. Entropy analyses revealed that the E1 protein was relatively variable among the HPV52 isolates, whereas the E7, E4, and L2 proteins showed some variations among the HPV58 isolates. Conclusions Among the HPV52/58-positive specimens from Japanese women with CIN/ICC, the variant distributions were strongly biased toward lineage B for HPV52 and lineage A for HPV58 across histological categories. Different patterns of amino acid variations were observed in HPV52 and HPV58 across the viral whole-genome.http://link.springer.com/article/10.1186/s13027-017-0155-4Human papillomavirusHPV52/58Cervical cancerVariantSNPs |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yuri Tenjimbayashi Mamiko Onuki Yusuke Hirose Seiichiro Mori Yoshiyuki Ishii Takamasa Takeuchi Nobutaka Tasaka Toyomi Satoh Tohru Morisada Takashi Iwata Shingo Miyamoto Koji Matsumoto Akihiko Sekizawa Iwao Kukimoto |
spellingShingle |
Yuri Tenjimbayashi Mamiko Onuki Yusuke Hirose Seiichiro Mori Yoshiyuki Ishii Takamasa Takeuchi Nobutaka Tasaka Toyomi Satoh Tohru Morisada Takashi Iwata Shingo Miyamoto Koji Matsumoto Akihiko Sekizawa Iwao Kukimoto Whole-genome analysis of human papillomavirus genotypes 52 and 58 isolated from Japanese women with cervical intraepithelial neoplasia and invasive cervical cancer Infectious Agents and Cancer Human papillomavirus HPV52/58 Cervical cancer Variant SNPs |
author_facet |
Yuri Tenjimbayashi Mamiko Onuki Yusuke Hirose Seiichiro Mori Yoshiyuki Ishii Takamasa Takeuchi Nobutaka Tasaka Toyomi Satoh Tohru Morisada Takashi Iwata Shingo Miyamoto Koji Matsumoto Akihiko Sekizawa Iwao Kukimoto |
author_sort |
Yuri Tenjimbayashi |
title |
Whole-genome analysis of human papillomavirus genotypes 52 and 58 isolated from Japanese women with cervical intraepithelial neoplasia and invasive cervical cancer |
title_short |
Whole-genome analysis of human papillomavirus genotypes 52 and 58 isolated from Japanese women with cervical intraepithelial neoplasia and invasive cervical cancer |
title_full |
Whole-genome analysis of human papillomavirus genotypes 52 and 58 isolated from Japanese women with cervical intraepithelial neoplasia and invasive cervical cancer |
title_fullStr |
Whole-genome analysis of human papillomavirus genotypes 52 and 58 isolated from Japanese women with cervical intraepithelial neoplasia and invasive cervical cancer |
title_full_unstemmed |
Whole-genome analysis of human papillomavirus genotypes 52 and 58 isolated from Japanese women with cervical intraepithelial neoplasia and invasive cervical cancer |
title_sort |
whole-genome analysis of human papillomavirus genotypes 52 and 58 isolated from japanese women with cervical intraepithelial neoplasia and invasive cervical cancer |
publisher |
BMC |
series |
Infectious Agents and Cancer |
issn |
1750-9378 |
publishDate |
2017-08-01 |
description |
Abstract Background Human papillomavirus genotypes 52 and 58 (HPV52/58) are frequently detected in patients with cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC) in East Asian countries including Japan. As with other HPV genotypes, HPV52/58 consist of multiple lineages of genetic variants harboring less than 10% differences between complete genome sequences of the same HPV genotype. However, site variations of nucleotide and amino acid sequences across the viral whole-genome have not been fully examined for HPV52/58. The aim of this study was to investigate genetic variations of HPV52/58 prevalent among Japanese women by analyzing the viral whole-genome sequences. Methods The entire genomic region of HPV52/58 was amplified by long-range PCR with total cellular DNA extracted from cervical exfoliated cells isolated from Japanese patients with CIN or ICC. The amplified DNA was subjected to next generation sequencing to determine the complete viral genome sequences. Phylogenetic analyses were performed with the whole-genome sequences to assign variant lineages/sublineages to the HPV52/58 isolates. The variability in amino acid sequences of viral proteins was assessed by calculating the Shannon entropy scores at individual amino acid positions of HPV proteins. Results Among 52 isolates of HPV52 (CIN1, n = 20; CIN2/3, n = 21; ICC, n = 11), 50 isolates belonged to lineage B (sublineage B2) and two isolates belonged to lineage A (sublineage A1). Among 48 isolates of HPV58 (CIN1, n = 21; CIN2/3, n = 19; ICC, n = 8), 47 isolates belonged to lineage A (sublineages A1/A2/A3) and one isolate belonged to lineage C. Single nucleotide polymorphisms specific for individual variant lineages were determined throughout the viral genome based on multiple sequence alignments of the Japanese HPV52/58 isolates and reference HPV52/58 genomes. Entropy analyses revealed that the E1 protein was relatively variable among the HPV52 isolates, whereas the E7, E4, and L2 proteins showed some variations among the HPV58 isolates. Conclusions Among the HPV52/58-positive specimens from Japanese women with CIN/ICC, the variant distributions were strongly biased toward lineage B for HPV52 and lineage A for HPV58 across histological categories. Different patterns of amino acid variations were observed in HPV52 and HPV58 across the viral whole-genome. |
topic |
Human papillomavirus HPV52/58 Cervical cancer Variant SNPs |
url |
http://link.springer.com/article/10.1186/s13027-017-0155-4 |
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