Clarification of liver condition progress mechanism that uses Hepatitis B virus reproduction model

• Project/Area Number: 20590789
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Nagoya City University
• Principal Investigator: TANAKA Yasuhito Nagoya City University, 大学院・医学研究科, 教授 (90336694)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: HBV / 肝発癌 / 共感染 / キメラマウス / 免疫不全 / トランスジェニックマウス / 遺伝子型 / コアプロモーター / コア蛋白質 / 遺伝子導入マウス / 肝線維化 / モデルマウス

Research Abstract

(1) Mechanism of hepatitis B virus (HBV) infection and replication : (1)HBV core protein as well as core promoter mutations are associated with viral replication. (2)The replication of genotype G was supported by core proteins of the other genotypes. (3)The hollow-fiber 3D culture system is superior to conventional monolayer culture allowing maintenance of HBV replication for a substantially longer duration. (2) Clarification of liver condition progress mechanism : Infection with HBV/C2 as well as PC mutant in immunosuppressive conditions can induce direct cytopathic effect in "humanized" part of the murine liver due to the activation of hepatic stellate cells mediated by oxidative stress.

Research Products

• [Journal Article] A genetic variant of hepatitis B virus divergent from known human and ape genotypes isolated from a Japanese patient and provisionally assigned to new genotype J. (2009)
  • Author(s): Tatematsu K, Tanaka Y, Mizokami M., (10人中2番目)
  • Journal Title: J Virol. 83(20) Pages: 10538-10547
  • Peer Reviewed
• [Journal Article] Case-control study for the identification of virological factors associated with fulminant hepatitis B. (2009)
  • Author(s): Kusakabe A, Tanaka Y, Mizokami M., (23人中2番目)
  • Journal Title: Hepatol Res. 39(7) Pages: 648-656
  • NAID: 10025326539
  • Peer Reviewed
• [Journal Article] Distribution of hepatitis B virus genotypes among patients with chronic infection in Japan shifting toward an increase of genotype A. (2009)
  • Author(s): Matsuura K, Tanaka Y, Mizokami M., (22人中2番目)
  • Journal Title: J Clin Microbiol. 47(5) Pages: 1476-1483
  • Peer Reviewed
• [Journal Article] Impact of determination of hepatitis B virus subgenotype and pre-core/core-promoter mutation for the prediction of acute exacerbation of asymptomatic carriers. (2009)
  • Author(s): Ikegami T, Matsuki Y, Tanaka Y, Matsuzaki Y., (8人中3番目)
  • Journal Title: Hepatol Res. 39(4) Pages: 341-345
  • NAID: 10025325326
  • Peer Reviewed
• [Journal Article] B型肝炎の治療最前線B型慢性肝炎に対するエンテカビル治療. (2009)
  • Author(s): 田中靖人, 向出雅一, 菅内文中, 溝上雅史
  • Journal Title: 臨床消化器内科 24(6) Pages: 691-699
• [Journal Article] 「イムニスHBVゲノタイプEIA」の基礎的・臨床的検討. (2009)
  • Author(s): 田中靖人, 菅内文中, 溝上雅史, (11人中1番目)
  • Journal Title: 臨床病理 24(6) Pages: 42-47
  • NAID: 10025224164
  • Peer Reviewed
• [Journal Article] Case-control study for the identification of virological factors associated with fulminant hepatitis B (2009)
  • Author(s): Kusakabe A.
  • Journal Title: Hepatol Res. 24 Pages: 691-699
  • Peer Reviewed
• [Journal Article] Distribution of hepatitis B virus genotypes among patients with chronic infection in Japan shifting toward an increase of genotype A (2009)
  • Author(s): Matsuura K.
  • Journal Title: J Clin Microbiol. 47 Pages: 1476-1483
  • Peer Reviewed
• [Journal Article] Genetic variant of hepatitis B virus divergent from known human andape genotypes isolated from a Japanese patient and provisionally assigned to new genotype J (2009)
  • Author(s): Tatematsu K.
  • Journal Title: J Virol. 83 Pages: 10538-10547
  • Peer Reviewed
• [Journal Article] Impact of determination of hepatitis B virus subgenotype and pre-core/core-promoter mutation for the prediction of acute exacerbation of asymptomatic carriers (2009)
  • Author(s): Ikegami T.
  • Journal Title: Hepatol Res. 39(4) Pages: 341-345
  • Peer Reviewed
• [Journal Article] B型肝炎の治療最前線 B型慢性肝炎に対するエンテカビル治療 (2009)
  • Author(s): 田中靖人
  • Journal Title: 臨床消化器内科 24 Pages: 691-699
• [Journal Article] 「イムニスHBVゲノタイプEIA」の基礎的・臨床的検討 (2009)
  • Author(s): 田中靖人
  • Journal Title: 臨床病理 57(1) Pages: 42-47
  • NAID: 10025224164
  • Peer Reviewed
• [Journal Article] Direct Cytopathic Effects of Particular Hepatitis B Virus Genotypes in sever combined immunodeficiency transgenic with urokinase-type plasminogen activator mouse with Human Hepatocytes. (2009)
  • Author(s): Sugiyama Masaya
  • Journal Title: Gastroenterolog 136(2) Pages: 652-662
  • Peer Reviewed
• [Journal Article] Detection of hepatitis C virus natural recombinant RF1_2k/1b strain among intravenous drug users in Uzbekistan. (2008)
  • Author(s): Kurbanov F, Tanaka Y, Mizokami M.. (10人中2番目)
  • Journal Title: Hepatol Res. 38(5) Pages: 457-464
  • NAID: 10024148344
  • Peer Reviewed
• [Journal Article] Characteristics of hepatitis B virus genotype G coinfected with genotype H in chimeric mice carrying human hepatocytes. (2008)
  • Author(s): Tanaka Y, Sugiyama M, Mizokami M., (11人中1番目)
  • Journal Title: Virology. 376(2) Pages: 408-15
  • Peer Reviewed
• [Journal Article] When should "I" consider a new hepatitis B virus genotype? (2008)
  • Author(s): Kurbanov F, Tanaka Y, Simmonds P, Mizokami M., (5人中2番目)
  • Journal Title: J Virol. 82(16) Pages: 8241-8242
  • Peer Reviewed
• [Journal Article] Characteristics of hepatitis B virus genotype G coinfected with genotype H in Chimeric Mice Carrying Human Hepatocytes (2008)
  • Author(s): Tanaka Yasuhito
  • Journal Title: Virology 376(2) Pages: 408-415
  • Peer Reviewed
• [Journal Article] When should"I"consider a new hepatitis B virus genotype? (2008)
  • Author(s): Kurbanov Fuat
  • Journal Title: Journal of Virology 82(16) Pages: 8241-8242
  • Peer Reviewed
• [Presentation] 変わり行くB型肝炎の臨床. (2009)
  • Author(s): 田中靖人
  • Organizer: 第304回日本消化器病学会関東支部例会
  • Place of Presentation: 海運クラブ(東京)
  • Year and Date: 2009-05-16
• [Presentation] 変わり行くB型肝炎の臨床 (2009)
  • Author(s): 田中靖人
  • Organizer: 第304回日本消化器病学会関東支部例会
  • Place of Presentation: 海運クラブ(東京)
  • Year and Date: 2009-05-16
• [Presentation] Complete genomic analyses of 153 hepatitis B virus genotype C2 strains in Japan reveal association of T1497V, C1653T and T1753V mutations with hepatocellular carcinoma. (2009)
  • Author(s): Shinkai Noboru
  • Organizer: 13th International Symposium on Viral Hepatitis and Liver Disease.
  • Place of Presentation: MARRIOTT WARDMAN PARK HOTEL (Washington DC, USA. )
  • Year and Date: 2009-03-24
• [Presentation] Direct Cytopathic Effects by Hepatitis B Virus Infection in uPA/SCID Mouse with Human Hepatocytes. (2009)
  • Author(s): Sugiyama Masaya
  • Organizer: 13th International Symposium on Viral Hepatitis and Liver Disease
  • Place of Presentation: MARRIOTT WARDMAN PARK HOTEL (Washington DC, USA. )
  • Year and Date: 2009-03-24
• [Presentation] Heterogeneity in HBV genotype distribution and high prevalence of occult hepatitis B in native Mexican population. (2009)
  • Author(s): Roman Sonia
  • Organizer: 13th International Symposium on Viral Hepatitis and Liver Disease.
  • Place of Presentation: MARRIOTT WARDMAN PARK HOTEL (Washington DC, USA. )
  • Year and Date: 2009-03-24
• [Presentation] Molecular epidemiology study of hepatitis B virus suggests origin of genotype G in Mexico. (2009)
  • Author(s): Panduro Arturo
  • Organizer: 13th International Symposium on Viral Hepatitis and Liver Disease
  • Place of Presentation: MARRIOTT WARDMAN PARK HOTEL (Washington DC, USA. )
  • Year and Date: 2009-03-24
• [Presentation] Complete genomic analyses of 153 hepatitis B virus genotype C2 strains in Japan reveal association of T1497V, C1653T and T1753Y mutations with hepatocellular carcinoma (2009)
  • Author(s): Shinkai Noboru
  • Organizer: 13th International Symposium on Viral Hepatitis and LiYer Disease
  • Place of Presentation: Washington DC
  • Year and Date: 2009-03-24
• [Presentation] Direct Cytopathic Effects by Hepatitis B Virus Infection in uPA/SCID Mouse with Human Hepatocytes (2009)
  • Author(s): Sugiyama Masaya
  • Organizer: 13th International Symposium on Viral Hepatitis and Liver Disease
  • Place of Presentation: Washington DC
  • Year and Date: 2009-03-24
• [Presentation] Heterogeneity in HBV genotype distribution and high prevalence of occult hepatitis Bin native Mexican population (2009)
  • Author(s): Roman Sonia
  • Organizer: 13th International Symposium on ViralHepatitis and Liver Disease
  • Place of Presentation: Washington DC
  • Year and Date: 2009-03-24
• [Presentation] Molecular epidemiology study of hepatitis B virus suggests origin of genotype G in Mexico (2009)
  • Author(s): Panduro Arturo
  • Organizer: 13th International Symposiui on Viral Hepatitis and Liver Disease
  • Place of Presentation: Washington DC
  • Year and Date: 2009-03-24
• [Presentation] Clinical and virological characteristics of Hepatitis B Virus Genotype E: key mutation in seroconversion, and similarity of regularatory sequence to genotype D. (2009)
  • Author(s): Fujiwara Kei
  • Organizer: 19th Conference of the Asian Pacific Association for the Study of the Liver
  • Place of Presentation: HONG KONG CONVENTION AND EXHIBITION CENTER (Hong Kong, CHINA)
  • Year and Date: 2009-02-13
• [Presentation] Distribution of Hepatitis B Virus Genotypes among Patients with Chronic Infection in Japan Shifting Toward an Increase of Genotype A. (2009)
  • Author(s): Matsuura Kentaroh
  • Organizer: 19th Conference of the Asian Pacific Association for the Study of the Liver
  • Place of Presentation: HONG KONG CONVENTION AND EXHIBITION CENTER (Hong Kong, CHINA)
  • Year and Date: 2009-02-13
• [Presentation] Clinical and virological characteristics of Hepatitis B Virus Genotype E : key mutation in seroconversion, and similarity of regularatory sequence to genotype D (2009)
  • Author(s): Fujiwara Kei
  • Organizer: 19th Conference of the Asian Pacific Association for the study of the Liver.
  • Place of Presentation: Hong Eong
  • Year and Date: 2009-02-13
• [Presentation] Distribution of Hepatitis B Virus Genotypes among Patients with Chronic Infection in Japan Shifting Toward an Increase of Genotype A (2009)
  • Author(s): Matsuura Kentaroh
  • Organizer: 19th Conference of the Asian Pacific Association for the study of the Liver.
  • Place of Presentation: Hong Kong
  • Year and Date: 2009-02-13
• [Presentation] B型肝炎に対するEntecavirの治療成績と各種血清マーカーの推移. (2009)
  • Author(s): 松浦健太郎
  • Organizer: 第38回日本肝臓学会西部会
  • Place of Presentation: 米子コンベンションセンター(米子)
• [Presentation] Identification of genetic variants associated with chronic hepatitis B or C in a genome-wide association. (2009)
  • Author(s): Matuura K.
  • Organizer: The 8th JSH Single Topic Conference
  • Place of Presentation: International Medical Center of Japan (Tokyo)
• [Presentation] Clinical significance of a novel high-sensitivity hepatitis B surface antigen immunoassay in patients with hepatitis B virus infection. (2009)
  • Author(s): Sugauchi F.
  • Organizer: 60th American Association for the Study of Liver Disease (AASLD)
  • Place of Presentation: HYNES CONVENTION CENTER (Boston MA, USA. )
• [Presentation] A genome-wide association study identifies genetic variants in the HLA-DP associated with chronic hepatitis B. (2009)
  • Author(s): Matsuura K.
  • Organizer: 60th American Association for the Study of Liver Disease (AASLD).
  • Place of Presentation: HYNES CONVENTION CENTER (Boston MA, USA. )
• [Presentation] B型肝炎ウイルス感染による肝細胞障害の機序. (2009)
  • Author(s): 田中靖人
  • 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)
• [Presentation] B型慢性肝炎難治例への対策B型肝炎に対するAdefovir、Entecavirの治療成績と多剤耐性HBV変異株に対するTenofovirの有効性. (2009)
  • Author(s): 菅内文中
  • Organizer: 第13回日本肝臓学会大会
  • Place of Presentation: 京都国際会議場(京都)
• [Presentation] コンセンサスミーティングB型肝炎:hbv遺伝子型と病態・予後. (2009)
  • Author(s): 田中靖人
  • Organizer: 第45回日本肝臓学会総会
  • Place of Presentation: 神戸ポートピアホテル(神戸)
• [Presentation] HBV genotype A, B, C, DにおけるHBs抗原定量の臨床的意義. (2009)
  • Author(s): 木村達治
  • Organizer: 第45回日本肝臓学会総会
  • Place of Presentation: 神戸ポートピアホテル(神戸)
• [Presentation] Clinical significance of a novel high-sensitivity hepatitis B surface antigen immunoassay in patients with hepatitis B virus infection (2009)
  • Author(s): 菅内文中
  • Organizer: 60th American Association for the Study of Liver Disease(AASLD)
  • Place of Presentation: Boston MA, USA
• [Presentation] A genome-wide association study identifies genetic variants in the HLA-DP associated with chronic hepatitis B (2009)
  • Author(s): 松浦健太郎
  • Organizer: 60th American Association for the Study of Liver Disease(AASLD)
  • Place of Presentation: Boston MA, USA
• [Presentation] Identification of genetic variants associated with chronic hepatitis B or C in a genome-wide association (2009)
  • Author(s): 松浦健太郎
  • Organizer: The 8^<th> JSH Single Topic Conference
  • Place of Presentation: International Medical Center of Japan(Tokyo)
• [Presentation] コンセンサスミーティングB型肝炎:HBV遺伝子型と病態・予後 (2009)
  • Author(s): 田中靖人
  • Organizer: 第45回日本肝臓学会総会
  • Place of Presentation: 神戸ポートピアホテル(神戸)
• [Presentation] HBV genotype A, B, C, DにおけるHBs抗原定量の臨床的意義 (2009)
  • Author(s): 木村達治
  • Organizer: 第45回日本肝臓学会総会
  • Place of Presentation: 神戸ポートピアホテル(神戸)
• [Presentation] B型慢性肝炎難治例への対策 B型肝炎に対する Adefovir、Entecavir の治療成績と多剤耐性HBV変異株に対する Tenofovir の有効性 (2009)
  • Author(s): 菅内文中
  • Organizer: 第13回日本肝臓学会大会
  • Place of Presentation: 京都国際会議場(京都)
• [Presentation] B型肝炎ウイルス感染による肝細胞障害の機序 (2009)
  • Author(s): 田中靖人
  • 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)
• [Presentation] B型肝炎に対する Entecavir の治療成績と各種血清マーカーの推移 (2009)
  • Author(s): 松浦健太郎
  • Organizer: 第38回日本肝臓学会西部会
  • Place of Presentation: 米子コンベンションセンター(米子)
• [Presentation] B型・C型肝炎ウイルスgenotyping/sequencingの臨床的意義. (2008)
  • Author(s): 田中靖人
  • Organizer: 第12回日本肝臓学会大会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-02
• [Presentation] B型・C型肝炎ウイルスgenotyping/sequencingの臨床的意義 (2008)
  • Author(s): 田中 靖人
  • Organizer: 第12回日本肝臓学会大会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-02