Comprehensive study of hepatitis B virus genotypes and mutations involved in the pathogenesis

• Project/Area Number: 22790627
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Tohoku University
• Principal Investigator: INOUE Jun 東北大学, 病院, 医員 (60455821)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 肝臓学 / ウイルス性肝炎

Research Abstract

To investigate hepatitis B virus (HBV)genotypes and mutations that are involved in the pathogenesis, full-genome analysis of genotype B1/Bj HBV, which is known to occur fulminant hepatitis frequently, was performed. Interestingly, single nucleotide insertion/deletion that causes frameshift in the precore region was found frequently in fulminant hepatitis strains. Furthermore, amino acid 21 mutation in the core protein was also found frequently. In vitro studies clarified that HBV with these insertion/deletion/mutation showed high replication capacity. These findings might clarify a part of fulminant hepatitis pathogenesis.

Research Products

• [Journal Article] Enhanced replication of hepatitis B virus with frameshift in the precore region found in fulminant hepatitis patients (2011)
  • Author(s): Inoue J, Ueno Y, Wakui Y, Fukushima K, Kondo Y, Kakazu E, Ninomiya M, Niitsuma H, Shimosegawa T
  • Journal Title: Infect Dis. Volume: 204 Pages: 1017-25
  • Peer Reviewed
• [Journal Article] B型劇症肝炎におけるgenotype, precore領域frameshiftの意義 (2011)
  • Author(s): 井上淳, 上野義之, 下瀬川徹
  • Journal Title: 消化器内科 Volume: 53 Pages: 595-600
  • Peer Reviewed
• [Journal Article] Enhanced replication of hepatitis B virus with frameshift in the precoreregion found in fulminant hepatitis patients (2011)
  • Author(s): Inoue J, Ueno Y, Wakui Y, Fukushima K, Kondo Y, Kakazu E, Ninomiya M, Niitsuma H, Shimosegawa T
  • Journal Title: The Journal of Infectious Diseases Volume: 204 Pages: 1017-1025
  • Peer Reviewed
• [Journal Article] Four-year study of lamivudine and adefovir combination therapy in lamivudine-resistant hepatitis B patients : Influence of hepatitis B virus genotype and resistance mutation pattern (2011)
  • Author(s): Inoue J, Ueno Y, Wakui Y, Niitsuma H, Fukushima K, Yamagiwa Y, Shiina M, Kondo Y, Kakazu E, Tamai K, Obara N, Iwasaki T, Shimosegawa T.
  • Journal Title: Journal of Viral Hepatitis Volume: 18 Pages: 206-215
  • Peer Reviewed
• [Journal Article] Management of chronic hepatitis B patients : Efficacy & limitation of nucleos(t)ide analogues (2011)
  • Author(s): Inoue J, Ueno Y, Shimosegawa T
  • Journal Title: Indian Journal of Medical Research Volume: 133 Pages: 11-14
  • Peer Reviewed
• [Journal Article] Inhibitory effect on hepatitis B virus in vitro by a peroxisome proliferator-activated receptor-γ ligand, rosiglitazone (2010)
  • Author(s): Wakui Y, Inoue J, Ueno Y, Fukushima K, Kondo Y, Kakazu E, Obara N, Kimura O, Shimosegawa T
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 396 Pages: 508-514
  • Peer Reviewed
• [Presentation] Yasuteru Kondo, Eiji Kakazu, Masashi Ninomiya, Osamu Kimura, Tooru Shimosegawa. Association between Mutations in a Cytotoxic T Lymphocyte Epitope of Hepatitis B Virus and Fulminant Hepatitis (2011)
  • Author(s): Jun Inoue, Yoshiyuki Ueno, Hirofumi Niitsuma
  • Organizer: The 62th Annual Meeting of the American Association for the Study of Liver Disease (AASLD)
  • Place of Presentation: サンフランシスコ, 米国
  • Year and Date: 2011-11-07
• [Presentation] Association between Mutations in a Cytotoxic T Lymphocyte Epitope of Hepatitis B Virus and Fulminant Hepatitis (2011)
  • Author(s): Jun Inoue, Yoshiyuki Ueno, Hirofumi Niitsuma, Yasuteru Kondo, Eiji Kakazu, Masashi Ninomiya, Osamu Kimura, Tooru Shimosegawa
  • Organizer: The 62th Annual Meeting of the American Association for the Study of Liver Disease (AASLD)
  • Place of Presentation: サンフランシスコ、米国
  • Year and Date: 2011-11-07
• [Presentation] Genotype B1/BjのHBVによる劇症肝炎とCTL epitope変異の関連 (2011)
  • Author(s): 井上淳, 上野義之, 涌井祐太, 福島耕治, 近藤泰輝, 嘉数英二, 二宮匡史, 新妻宏文, 三浦雅人, 下瀬川徹
  • Organizer: 第47回日本肝臓学会総会
  • Place of Presentation: 東京
  • Year and Date: 2011-06-02
• [Presentation] The Significance of Frameshift in the Precore Region of Hepatitis B Virus Obtained from Fulminant Hepatitis Patients (2010)
  • Author(s): Jun Inoue, Yoshiyuki Ueno, Yuta Wakui, Koji Fukushima, Yasuteru Kondo, Eiji Kakazu, Masashi Ninomiya, Hirofumi Niitsuma, Tooru Shimosegawa
  • Organizer: The 61th Annual Meeting of the American Association for the Study of Liver Disease (AASLD)
  • Place of Presentation: ボストン, 米国
  • Year and Date: 2010-11-01
• [Presentation] The Significance of Frameshift in the Precore Region of Hepatitis B Virus Obtained from Fulminant Hepatitis Patients (2010)
  • Author(s): Jun Inoue, Yoshiyuki Ueno, Yuta Wakui, Koji Fukushima, Yasuteru Kondo, Eiji Kakazu, Masashi Ninomiya, Hirofumi Niitsuma, Tooru Shimosegawa
  • Organizer: The 61th Annual Meeting of the American Association for the Study of Liver Disease (AASLD)
  • Place of Presentation: ボストン、米国
  • Year and Date: 2010-11-01
• [Presentation] B型劇症肝炎におけるgenotype, precore領域frameshiftの意義 (2010)
  • Author(s): 井上淳, 上野義之, 下瀬川徹
  • Organizer: 第14回日本肝臓学会大会(JDDW2010)
  • Place of Presentation: 横浜
  • Year and Date: 2010-10-15
• [Presentation] B型劇症肝炎におけるgenotype,precore領域frameshiftの意義 (2010)
  • Author(s): 井上淳, 上野義之, 下瀬川徹
  • Organizer: 第14回日本肝臓学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2010-10-15