Whole-Genome Analysis of Human Papillomavirus Type 16 Prevalent in Japanese Women with or without Cervical Lesions
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Samples
2.2. Viral Whole-Genome Amplification and Next Generation Sequencing
2.3. Phylogenetic Tree Construction
2.4. Sequencing of HPV16 E6/E7
2.5. Generation of Human Cervical Keratinocytes Expressing E7
2.6. Western Blotting
2.7. Statistical Analysis
3. Results
3.1. Determination of HPV16 Whole-Genome Sequences from Japanese Women
3.2. Phylogenetic Analysis of Japanese HPV16 Isolates
3.3. Risk Assessment of HPV16 Variants for Cervical Cancer Development
3.4. Genetic Variability among Sublineage A4 Variants
3.5. Identification of SNPs Unique for A5 Variants
3.6. HPV16 Variant Distribution in Cervical Adenocarcinoma
3.7. Biological Activity of E7 Variants of Lineage A
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Variant | Total | NILM | CIN1 | CIN2/3 | ICC |
---|---|---|---|---|---|
All | 100 | 22 | 13 | 24 | 41 |
A | 94 | 21 | 11 | 24 | 38 |
A1 | 21 | 3 | 3 | 12 | 3 |
A2 | 2 | 0 | 2 | 0 | 0 |
A3 | 3 | 1 | 0 | 0 | 2 |
A4 | 52 | 10 | 4 | 8 | 30 |
A5 | 16 | 7 | 2 | 4 | 3 |
B | 0 | 0 | 0 | 0 | 0 |
C | 2 | 0 | 1 | 0 | 1 |
D | 4 | 1 | 1 | 0 | 2 |
D1 | 1 | 0 | 1 | 0 | 0 |
D2 | 1 | 0 | 0 | 0 | 1 |
D3 | 2 | 1 | 0 | 0 | 1 |
Variant | NILM/CIN1 | CIN2/3 | SCC | OR * (95% CI) | OR ** (95% CI) |
---|---|---|---|---|---|
All | 22 | 22 | 32 | ||
A1/2/3 | 8 | 11 | 5 | 1.00 (reference) | 1.00 (reference) |
A4 | 8 | 7 | 24 | 0.66 (0.16–2.62) | 6.72 (1.78–28.9) |
A5 | 4 | 4 | 2 | 0.77 (0.13–4.41) | 0.07 (0.0003–1.83) |
D1 | 1 | 0 | 0 | ND | ND |
D3 | 1 | 0 | 1 | ND | ND |
Region | Size (bp) | SNPs | Variable Sites (%) * | Synonymous | Non-Synonymous |
---|---|---|---|---|---|
All | 7905 ** | 142 | 1.80 | 57 | 60 |
E6 | 477 | 6 | 1.26 | 3 | 3 |
E7 | 297 | 4 | 1.35 | 4 | 0 |
E1 | 1950 | 17 | 0.87 | 11 | 6 |
E2 | 1098 | 17 | 1.55 | 4 | 13 |
E4 | 288 | 7 | 2.43 | 4 | 3 |
E5 | 252 | 9 | 3.57 | 1 | 8 |
NC | 134 | 10 | 7.46 | ||
L2 | 1422 | 37 | 2.60 | 16 | 21 |
L1 | 1596 | 20 | 1.25 | 14 | 6 |
LCR | 832 | 22 | 2.64 |
Position * | A5 | Others | Gene | Position ** | A5 | Others |
---|---|---|---|---|---|---|
645 | C | A | E7 | 28 | Phe | Leu |
3068 | A | G | E2 | 105 | Thr | Ala |
4458 | C | A | L2 | 74 | Pro | Pro |
5042 | A | C | L2 | 269 | Asp/Asn | Ser/Pro/Ala |
5836 | G | A | L1 | 92 | Ser | Ser |
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Hirose, Y.; Onuki, M.; Tenjimbayashi, Y.; Yamaguchi-Naka, M.; Mori, S.; Tasaka, N.; Satoh, T.; Morisada, T.; Iwata, T.; Kiyono, T.; et al. Whole-Genome Analysis of Human Papillomavirus Type 16 Prevalent in Japanese Women with or without Cervical Lesions. Viruses 2019, 11, 350. https://doi.org/10.3390/v11040350
Hirose Y, Onuki M, Tenjimbayashi Y, Yamaguchi-Naka M, Mori S, Tasaka N, Satoh T, Morisada T, Iwata T, Kiyono T, et al. Whole-Genome Analysis of Human Papillomavirus Type 16 Prevalent in Japanese Women with or without Cervical Lesions. Viruses. 2019; 11(4):350. https://doi.org/10.3390/v11040350
Chicago/Turabian StyleHirose, Yusuke, Mamiko Onuki, Yuri Tenjimbayashi, Mayuko Yamaguchi-Naka, Seiichiro Mori, Nobutaka Tasaka, Toyomi Satoh, Tohru Morisada, Takashi Iwata, Tohru Kiyono, and et al. 2019. "Whole-Genome Analysis of Human Papillomavirus Type 16 Prevalent in Japanese Women with or without Cervical Lesions" Viruses 11, no. 4: 350. https://doi.org/10.3390/v11040350
APA StyleHirose, Y., Onuki, M., Tenjimbayashi, Y., Yamaguchi-Naka, M., Mori, S., Tasaka, N., Satoh, T., Morisada, T., Iwata, T., Kiyono, T., Mimura, T., Sekizawa, A., Matsumoto, K., & Kukimoto, I. (2019). Whole-Genome Analysis of Human Papillomavirus Type 16 Prevalent in Japanese Women with or without Cervical Lesions. Viruses, 11(4), 350. https://doi.org/10.3390/v11040350