Whole-genome analysis of human papillomavirus genotypes 52 and 58 isolated from Japanese women with cervical intraepithelial neoplasia and invasive cervical cancer

Yuri Tenjimbayashi, Mamiko Onuki, Yusuke Hirose, Seiichiro Mori, Yoshiyuki Ishii, Takamasa Takeuchi, Nobutaka Tasaka, Toyomi Satoh, Toru Morisada, Takashi Iwata, Shingo Miyamoto, Koji Matsumoto, Akihiko Sekizawa, Iwao Kukimoto

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article number44
JournalInfectious Agents and Cancer
Volume12
Issue number1
DOIs
Publication statusPublished - 2017 Aug 4

Fingerprint

Cervical Intraepithelial Neoplasia
Human Genome
Uterine Cervical Neoplasms
Genotype
Viral Genome
Entropy
Genome
Amino Acid Sequence
Amino Acids
Proteins
Sequence Alignment
DNA
Viral Proteins
varespladib methyl
Single Nucleotide Polymorphism
Japan
Nucleotides

Keywords

  • Cervical cancer
  • HPV52/58
  • Human papillomavirus
  • SNPs
  • Variant

ASJC Scopus subject areas

  • Epidemiology
  • Oncology
  • Cancer Research
  • Infectious Diseases

Cite this

Whole-genome analysis of human papillomavirus genotypes 52 and 58 isolated from Japanese women with cervical intraepithelial neoplasia and invasive cervical cancer. / Tenjimbayashi, Yuri; Onuki, Mamiko; Hirose, Yusuke; Mori, Seiichiro; Ishii, Yoshiyuki; Takeuchi, Takamasa; Tasaka, Nobutaka; Satoh, Toyomi; Morisada, Toru; Iwata, Takashi; Miyamoto, Shingo; Matsumoto, Koji; Sekizawa, Akihiko; Kukimoto, Iwao.

In: Infectious Agents and Cancer, Vol. 12, No. 1, 44, 04.08.2017.

Research output: Contribution to journalArticle

Tenjimbayashi, Y, Onuki, M, Hirose, Y, Mori, S, Ishii, Y, Takeuchi, T, Tasaka, N, Satoh, T, Morisada, T, Iwata, T, Miyamoto, S, Matsumoto, K, Sekizawa, A & Kukimoto, I 2017, '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, vol. 12, no. 1, 44. https://doi.org/10.1186/s13027-017-0155-4
Tenjimbayashi, Yuri ; Onuki, Mamiko ; Hirose, Yusuke ; Mori, Seiichiro ; Ishii, Yoshiyuki ; Takeuchi, Takamasa ; Tasaka, Nobutaka ; Satoh, Toyomi ; Morisada, Toru ; Iwata, Takashi ; Miyamoto, Shingo ; Matsumoto, Koji ; Sekizawa, Akihiko ; Kukimoto, Iwao. / Whole-genome analysis of human papillomavirus genotypes 52 and 58 isolated from Japanese women with cervical intraepithelial neoplasia and invasive cervical cancer. In: Infectious Agents and Cancer. 2017 ; Vol. 12, No. 1.
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T1 - Whole-genome analysis of human papillomavirus genotypes 52 and 58 isolated from Japanese women with cervical intraepithelial neoplasia and invasive cervical cancer

AU - Tenjimbayashi, Yuri

AU - Onuki, Mamiko

AU - Hirose, Yusuke

AU - Mori, Seiichiro

AU - Ishii, Yoshiyuki

AU - Takeuchi, Takamasa

AU - Tasaka, Nobutaka

AU - Satoh, Toyomi

AU - Morisada, Toru

AU - Iwata, Takashi

AU - Miyamoto, Shingo

AU - Matsumoto, Koji

AU - Sekizawa, Akihiko

AU - Kukimoto, Iwao

PY - 2017/8/4

Y1 - 2017/8/4

N2 - 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.

AB - 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.

KW - Cervical cancer

KW - HPV52/58

KW - Human papillomavirus

KW - SNPs

KW - Variant

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