Are APOBEC deaminases oncogenic in HPV infection?

• Project/Area Number: 26861318
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Kanazawa University
• Principal Investigator: Wakae Kousho 金沢大学, 医学系, 助教 (70638303)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: APOBEC / 子宮頸癌 / hypermutation / HPV / ヒトパピローマウイルス / 変異 / pseudovirion

Outline of Final Research Achievements

This study aimed to clarify the pathophysiological role of APOBEC deaminases in HPV infection. We obtained the following conclusion. 1. APOBECs are induced by interferons and HPV 2. APOBECs hypermutate HPV or host genomes, and their expression correlates with integration of HPV genome into the host 3. On the contrary, APOBECs decrease infectivity of HPV virion when expressed in virion-producing cells. These finding revealed the bilateral role of APOBECs as antiviral and oncogenic molecules, in HPV infection.

Research Products

• [Journal Article] APOBEC3A Associates with Human Papillomavirus Genome Integration in Oropharyngeal Cancers (2017)
  • Author(s): Satoru Kondo, Kousho Wakae, Naohiro Wakisaka, Yosuke Nakanishi, Kazuya Ishikawa, Takeshi Komori, Makiko Moriyama-Kita, Kazuhira Endo, Shigeyuki Murono, Zhe Wang,, Kouichi Kitamura, Tomoaki Nishiyama, Katsushi Yamaguchi, Shuji Shigenobu, Masamichi Muramatsu, and Tomokazu Yoshizaki
  • Journal Title: Oncogene. Volume: 36 Issue: 12 Pages: 1687-1697
  • DOI: 10.1038/onc.2016.335
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] TGF-beta Suppression of HBV RNA through AID-Dependent Recruitment of an RNA Exosome Complex (2015)
  • Author(s): Liang, G., Liu, G., Kitamura, K., Wang, Z., Chowdhury, S., Monjurul, A. M., Wakae, K., Koura, M., Shimadu, M., Kinoshita, K., and Muramatsu, M.
  • Journal Title: PLoS Pathog. Volume: 11 Issue: 4 Pages: e1004780-e1004780
  • DOI: 10.1371/journal.ppat.1004780
  • Peer Reviewed / Open Access
• [Journal Article] Hypermutation in the E2 gene of human papillomavirus type 16 in cervical intraepithelial neoplasia. (2015)
  • Author(s): Kukimoto I, Mori S, Aoyama S, Wakae K, Muramatsu M, Kondo K.
  • Journal Title: Journal of Medical Virology Volume: 87 Issue: 10 Pages: 1754-1760
  • DOI: 10.1002/jmv.24215
  • Peer Reviewed
• [Journal Article] Detection of hypermutated human papillomavirus type 16 genome by Next-Generation Sequencing. (2015)
  • Author(s): Wakae K, Aoyama S, Wang Z, Kitamura K, Liu G, Monjurul AM, Koura M, Imayasu M, Sakamoto N, Nakamura M, Kyo S, Kondo S, Fujiwara H, Yoshizaki T, Kukimoto I, Yamaguchi K, Shigenobu S, Nishiyama T, Muramatsu M.
  • Journal Title: Virology Volume: 485 Pages: 460-466
  • DOI: 10.1016/j.virol.2015.08.017
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] APOBEC3A and 3C decrease human papillomavirus 16 pseudovirion infectivity. (2015)
  • Author(s): Ahasan MM, Wakae K, Wang Z, Kitamura K, Liu G, Koura M, Imayasu M, Sakamoto N, Hanaoka K, Nakamura M, Kyo S, Kondo S, Fujiwara H, Yoshizaki T, Mori S, Kukimoto I, Muramatsu M.
  • Journal Title: Biochem Biophys Res Commun. Volume: 457 Issue: 3 Pages: 295-9
  • DOI: 10.1016/j.bbrc.2014.12.103
  • Peer Reviewed / Open Access
• [Journal Article] Hypermutation in the E2 Gene of Human Papillomavirus Type 16 in Cervical Intraepithelial Neoplasia (2015)
  • Author(s): Iwao kukimoto, Seiichiro Mori, Satoru aoyama, Kosho Wakae, Masamichi Muramatsu, Kazunari Kondo
  • Journal Title: Journal of Medical Virology Volume: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Role of APOBEC3 in HPV-related carcinogenesis (2017)
  • Author(s): Kousho Wakae, Que Lusheng, Md Mohiuddin, Kouichi Kitamura, Wang Zhe, Takashi Izuka, Mitsuhiro Nakamura, Hiroshi Fujiwara, Satoru Kondo, Tomokazu Yoshizaki, Tomoaki Nishiyama, and Masamichi Muramatsu
  • Organizer: International Symposium on Immune Diversity and Cancer Therapy Kobe
  • Place of Presentation: 神戸ポートピアホテル（兵庫県神戸市）
  • Year and Date: 2017-01-26
  • Int'l Joint Research
• [Presentation] APOBEC3はHPV16感染細胞のミトコンドリアDNAにhypermutationを導入する (2016)
  • Author(s): 若江 亨祥、Que Lusheng、喜多村 晃一、飯塚 崇、中村 充弘、藤原 浩、近藤 悟、吉崎 智一、柊元 巌、西山 智明、村松 正道
  • Organizer: 第39回分子生物学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-11-30
• [Presentation] APOBEC3 hypermutates mitochondrial DNA in differentiating dysplastic keratinocytes (2016)
  • Author(s): Kousho Wakae, Que Lusheng、Kouichi Kitamura, Takashi Izuka, Mitsuhiro Nakamura, Hiroshi Fujiwara, Satoru Kondo, Tomokazu Yoshizaki, Tomoaki Nishiyama, and Masamichi Muramatsu
  • Organizer: The 13th Conference of Asian Society for Mitochondrial Research and Medicine / The 16th Conference of Japanese Society of Mitochondrial Research and Medicine
  • Place of Presentation: TKPガーデンシティ品川（東京都港区）
  • Year and Date: 2016-10-30
  • Int'l Joint Research
• [Presentation] ヒトパピローマウイルス発癌病態における遺伝子改編酵素群APOBECの役割 (2015)
  • Author(s): 若江 亨祥、青山 慧、王 哲、喜多村 晃一、劉 光炎、アハサン・ムハンマド・モンジュルル、小浦 美樹、今康 美依子、坂本 直也、中村 充広、京 哲、近藤 悟、 藤原 浩、吉崎 智一、柊元 巌、山口 勝司、重信 秀治、西山 智明、村松 正道
  • Organizer: 第２回ライフサイエンス交流交流セミナー
  • Place of Presentation: 金沢大学付属病院
  • Year and Date: 2015-12-08
• [Presentation] Epsilon RNA is required for AID-mediated reduction of HBV transcripts (2015)
  • Author(s): Que Lusheng, Kousho Wakae, Koichi Kitamura, Masamichi Muramatsu
  • Organizer: BMB 2015
  • Place of Presentation: 神戸国際展示場
  • Year and Date: 2015-12-01
• [Presentation] Epsilon RNA plays an important role for AID-mediated downregulation of HBV transcripts (2015)
  • Author(s): Liu Guangyan, Kousho Wakae, Koichi Kitamura, Masamichi Muramatsu
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2015-11-22
• [Presentation] APOBEC3Hの多型とB型肝炎ウイルス複製阻害活性の検討 (2015)
  • Author(s): 坂本直也、若江亨祥、喜多村晃一、村松正道
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2015-11-22
• [Presentation] Next Generation Sequencing detects APOBCEC3 mediated Hypermutation in Human Papillomavirus Type 16 Genome in vivo (2015)
  • Author(s): Kosho Wakae, Mitsuhiro Nakamura, Satoru Kondo, Hiroshi Fujiwara, Tomokazu Yoshizaki, Iwao Kukimoto, Tomoaki Nishiyama, and Masamichi Muramatsu
  • Organizer: 2015 DNA tumor virus Meeting
  • Place of Presentation: Congress Centre of the Stazione Marittina, Italy
  • Year and Date: 2015-07-24
  • Int'l Joint Research
• [Presentation] 子宮頸部異形成におけるHPV16ゲノム hypermutationの検出 (2015)
  • Author(s): 若江 亨祥, 青山 慧, 王 哲, 喜多村 晃一, 劉 光炎, アハサン=ムハンマド=モンジュルル, 中村 充宏, 藤原 浩, 柊元 巌, 山口 勝司, 重信 秀治, 西山 智明, 村松 正道
  • Organizer: 次世代シーケンス現場の会
  • Place of Presentation: つくば国際会議場
  • Year and Date: 2015-07-01
• [Presentation] APOBEC3はHPV16 Pseudovirionの感染性を低下させる (2015)
  • Author(s): 若江亨祥、Ahasan M Monjurul、王哲、喜多村晃一、森清一郎、柊元巌、中村充宏、藤原浩、村松正道
  • Organizer: 第３３回生化学会北陸支部大会
  • Place of Presentation: 富山大学杉谷キャンパス
  • Year and Date: 2015-05-23
• [Presentation] Role of APOBEC3 in HPV expressing cell (2015)
  • Author(s): Ahasan Monjurul, Kosho Wakae and Masamichi Muramatsu
  • Organizer: Japan Cancer Society Symposium
  • Place of Presentation: ANA CROWN Plaza Kanazawa
  • Year and Date: 2015-01-21 – 2015-01-22
• [Presentation] AID-dependent down-regulation of HBV transcripts (2015)
  • Author(s): Guangyan Liu,Guoxin Liang, Kouichi Kitamura, Zhe Wang, Sajeda Chowdhury, Miki Koura, Kosho Wakae and Masamichi Muramatsu
  • Organizer: Japan Cancer Society Symposium
  • Place of Presentation: ANA CROWN Plaza Kanazawa
  • Year and Date: 2015-01-21 – 2015-01-22
• [Presentation] APOBEC3 suppresses infectivity of HPV pseudovirion (2014)
  • Author(s): Ahasan Monjurul, Kosho Wakae and Masamichi Muramatsu
  • Organizer: The 43rd Annual Meeting of The Japanese Society for Immunology
  • Place of Presentation: Kyoto International Conference Center
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] APOBEC3はHPV16 Pseudovirionの感染性を低下させる (2014)
  • Author(s): 若江亨祥、Ahasan M Monjurul、王哲、喜多村晃一、森清一郎、柊元巌、中村充弘、藤原浩、村松正道
  • Organizer: 第６２回日本ウイルス学会学術集会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] A novel antiviral function of activation-induced cytidine deaminase downregulates hepatitis B viral RNA through recruitment of the RNA exosome complex (2014)
  • Author(s): Guangyan Liu, Guoxin Liang, Kouichi Kitamura, Zhe Wang, Sajeda Chowdhury, Miki Koura, Kosho Wakae and Masamichi Muramatsu
  • Organizer: 第87回 日本生化学会大会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-10-17 – 2014-10-18
• [Remarks] 研究室ホームページ
  • URL: http://molgenet.w3.kanazawa-u.ac.jp/home.html