Association of anti-hepatitis B virus pathway with carcinogenesis

• Project/Area Number: 21790654
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Kanazawa University
• Principal Investigator: KITAMURA Kouichi Kanazawa University, 医学系, 助教 (70378892)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ウイルス / がん / ゲノム / 免疫学 / ウィルス / 癌

Research Abstract

Human APOBEC3 proteins are reported to be antiviral factors and catalyze C-to-U conversion on hepatitis B virus (HBV) DNA by cytosine deamination. Extensive G-to-A hypermutation on plus-strand of HBV DNA has been observed from APOBEC3G-expressing hepatoma cells. We investigated whether UNG also process the hypermutated HBV genome with base excision activity. We found that the UNG inhibition caused accumulation of hypermutation in nuclear cccDNA and decrease of cytoplasmic rcDNA level. Sequencing analysis showed that some of these cccDNA mutations resulted in nonsense codons within viral polymerase coding region. These results suggest that the BER pathway triggered from nuclear UNG repairs the viral DNA mutations introduced by the antiviral APOBECs.

Research Products

• [Presentation] Uracil DNA Glycosylase Counteracts G to A Hypermutation of Hepatitis B Virus (2011)
  • Author(s): 喜多村晃一
  • Organizer: The 2011 Gordon Research Conference on RNA editing
  • Place of Presentation: Hotel Galvez (USA)
• [Presentation] Base excision repair by ur acil DNA glycosylase counteracts interf eron-induced hypermutation on hepatiti s B virus DNA (2010)
  • Author(s): 喜多村晃一
  • Organizer: 第14回国際免疫学会議
  • Place of Presentation: 神戸国際展示場(兵庫県)
  • Year and Date: 2010-08-24
• [Presentation] Base excision repair by uracil DNA glycosylase counteracts interferon-induced hypermutation on hepatitis B virus DNA (2010)
  • Author(s): 喜多村晃一
  • Organizer: 第14回国際免疫学会議
  • Place of Presentation: 神戸国際展示場(兵庫県)
  • Year and Date: 2010-08-24
• [Presentation] B型肝炎ウイルス高頻度突然変異における塩基除去修復因子UNG の作用 (2010)
  • Author(s): 喜多村晃一
  • Organizer: 日本生化学会 北陸支部第28回大会
  • Place of Presentation: 福井大学(福井県)
  • Year and Date: 2010-05-29
• [Presentation] B型肝炎ウイルス高頻度突然変異における塩基除去修復因子UNGの作用 (2010)
  • Author(s): 喜多村晃一
  • Organizer: 日本生化学会 北陸支部第28回大会
  • Place of Presentation: 福井大学(福井県)
  • Year and Date: 2010-05-29
• [Presentation] Effects of APOBEC3G and Base Excision Repair on Hepatitis BViral Genome (2009)
  • Author(s): 喜多村晃一
  • Place of Presentation: 大阪国際会議場(大阪府)
  • Year and Date: 2009-12-03
• [Presentation] Effects of APOBEC3G and Base Excision Repair on Hepatitis B Viral Genome (2009)
  • Author(s): 喜多村晃一
  • Organizer: 第39回日本免疫学会学術集会
  • Place of Presentation: 大阪国際会議場(大阪府)
  • Year and Date: 2009-12-03
• [Presentation] B型肝炎ウイルスに対するAPOBEC3Gと塩基除去修復因子の作用 (2009)
  • Author(s): 喜多村晃一
  • Organizer: 第57回日本ウイルス学会学術集会
  • Place of Presentation: 都市センターホテル(東京都)
  • Year and Date: 2009-10-25
• [Remarks]
  • URL: http://web.kanazawa-u.ac.jp/~med06/index.html
• [Remarks]
  • URL: http://web.kanazawa-u.ac.jp/~med06/index.html