Analysis ofchronic viral hepaptis by the large-scale next generation sequeincing

• Project/Area Number: 21659186
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: University of Yamanashi
• Principal Investigator: ENOMOTO Nobuyuki 山梨大学, 大学院・医学工学総合研究部, 教授 (20251530)
• Co-Investigator(Kenkyū-buntansha): MAEKAWA Shinya 山梨大学, 大学院・医学工学総合研究部, 講師 (70397298)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,300,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,000,000 (Direct Cost: ¥1,000,000); Fiscal Year 2009: ¥1,000,000 (Direct Cost: ¥1,000,000)
• Keywords: HCV / HBV / 次世代シークエンス / deep sequencing / シークエンス

Research Abstract

We developed the analytical method of rapid and large sccale sequenging of hepatitis virus genome in the patients with the next generation sequencer Roche Genome Sequencer Junior(GSJ), and revealed the dynamic changes of viral quasispcies constitution during the treatment and disease progression by the analysis of HCV core, NS3, NS5A genes and HBV pre S gene through deep sequencing.

Research Products

• [Journal Article] Correlation between Pretreatment Viral Sequences and the Emergence of Lamivudine Resistance in Hepatitis B Virus Infection. (2012)
  • Author(s): Sueki R, Maekawa S, Miura M, Kadokura M, Komase K, Shindo H, Kanayama A, Ohmori T, Shindo K, Amemiya F, Nakayama Y, Uetake T, Inoue T, Sakamoto M, Enomoto N.
  • Journal Title: J Med Virol Volume: (in press)
  • Peer Reviewed
• [Journal Article] Causes of Thrombocytopenia in Chronic Hepatitis C Viral Infection (2012)
  • Author(s): Osada M
  • Journal Title: Clin Appl Thromb Hemost Volume: 12(Epub ahead of print) Issue: 3 Pages: 272-280
  • DOI: 10.1177/1076029611429124
  • Peer Reviewed
• [Journal Article] Association of gene expression involving innate immunity and genetic variation in IL28B with antiviral response (2011)
  • Author(s): Asahina Y, Sakamoto N, et al
  • Journal Title: Hepatology Volume: 55(1) Issue: 1 Pages: 20-29
  • DOI: 10.1002/hep.24623
  • Peer Reviewed
• [Journal Article] Pre-treatment prediction of response to pegylated-interferon plus ribavirin forchronic hepatitis C using genetic polymorphism in IL28B and viral factors. (2011)
  • Author(s): Kurosaki M, Tanaka Y, Nishida N, SakamotoN, Enomoto N, Honda M, Sugiyama M, Matsuura K, Sugauchi F, Asahina Y, NakagawaM, Watanabe M, Sakamoto M, Maekawa S, SakaiA, Kaneko S, Ito K, Masaki N, Tokunaga K, Izumi N, Mizokami M.
  • Journal Title: J Hepatol Volume: 54(3) Pages: 439-48
  • Peer Reviewed
• [Journal Article] Analysis of the complete open reading frame of hepatitis C virus in genotype 2ainfection reveals critical sites influencing the response to peginterferon andribavirin therapy. (2011)
  • Author(s): Kadokura M, Maekawa S, Sueki R, Miura M, Komase K, Shindo H, Amemiya F, Uetake T, Inoue T, Sakamoto M, Nakagawa M, SakamotoN, Watanabe M, Enomoto N.
  • Journal Title: Hepatol Int Volume: 5(3) Pages: 789-99
  • Peer Reviewed
• [Journal Article] Relationship between polymorphisms of theinosine triphosphatase geneand anaemia or outcome after treatment with pegylated interferon and ribavirin. (2011)
  • Author(s): Kurosaki M, Tanaka Y, Tanaka K, Suzuki Y, Hoshioka Y, Tamaki N, Kato T, Yasui Y, Hosokawa T, Ueda K, Tsuchiya K, Kuzuya T, Nakanishi H, Itakura J, Takahashi Y, Asahina Y, Matsuura K, Sugauchi F, Enomoto N, Nishida N, Tokunaga K, Mizokami M, Izumi N.
  • Journal Title: Antivir Ther Volume: 16(5) Pages: 685-94
  • Peer Reviewed
• [Journal Article] Analysis of the complete open reading frame of genotype 2b hepatitis C virus inassociation with the response to peginterferon and ribavirin therapy. (2011)
  • Author(s): Kadokura M, Maekawa S, Sueki R, Miura M, Komase K, Shindo H, Amemiya F, UetakeT, Inoue T, Sakamoto M, Nakagawa M, SakamotoN, Watanabe M, Enomoto N.
  • Journal Title: PLoS One Volume: 6(9)
  • Peer Reviewed
• [Journal Article] Characterization of naturally occurring proteaseinhibitor-resistance mutations in genotype 1b hepatitis C virus patients. (2011)
  • Author(s): Shindo H, Maekawa S, Komase K, Sueki R, Miura M, Kadokura M, Shindo K, Amemiya F, Kitamura T, Nakayama Y, Inoue T, Sakamoto M, Okada SI, Asahina Y, Izumi N, Honda M, Kaneko S, Enomoto N.
  • Journal Title: Hepatol Int
  • Peer Reviewed
• [Journal Article] Analysis of viral amino acids sequences and the IL28B SNP in fluencing the development of hepatocellular carcinoma in chronic hepatitis C. (2011)
  • Author(s): Miura M, Maekawa S, Kadokura M, Sueki R, Komase K, Shindo H, Ohmori T, Kanayama A, Shindo K, Amemiya F, Nakayama Y, Kitamura T, Uetake T, Inoue T, Sakamoto M, Okada S, Enomoto N
  • Journal Title: Hepatol Int
  • Peer Reviewed
• [Journal Article] Analysis of viral amino acids sequences and the IL28B SNP influencing the development of hepatocellular carcinoma in chronic hepatitis C (2011)
  • Author(s): Miura M, Maekawa S, et.al
  • Journal Title: Hepatol Int. Volume: 6 Issue: 1 Pages: 386-396
  • DOI: 10.1007/s12072-011-9307-6
  • Peer Reviewed
• [Journal Article] Characterization of naturally occurring protease inhibitor-resistance mutations in genotype 1b hepatitis C virus patients (2011)
  • Author(s): Honda M, (他17名, 16番目)
  • Journal Title: Hepatol Int Epub ahead of print Volume: 2 Issue: 2 Pages: 482-490
  • DOI: 10.1007/s12072-011-9306-7
  • Peer Reviewed
• [Journal Article] A new method for induced fit docking (GENIUS) and its application to virtual screening of novel HCV NS3-4A protease inhibitors (2011)
  • Author(s): Takaya D, Sakamoto N, et al.
  • Journal Title: Bioorganic & Medicinal Chemistry Volume: 19(22) Issue: 22 Pages: 6892-6905
  • DOI: 10.1016/j.bmc.2011.09.023
  • Peer Reviewed
• [Journal Article] Analysis of the complete open reading frame of genotype 2b hepatitis C virus in association with the response to peginterferon and ribavirin therapy (2011)
  • Author(s): Kadokura M, Nakagawa M, Sakamoto N, Watanabe M, et al.
  • Journal Title: PLoS One Volume: 6(9) Issue: 9 Pages: e24514-e24514
  • DOI: 10.1371/journal.pone.0024514
  • Peer Reviewed
• [Journal Article] Will there be an HCV meeting in 2020? Summary of the 17th international meeting on hepatitis C virus and related viruses (2011)
  • Author(s): Wakita T
  • Journal Title: Gastroenterology Volume: 141
  • Peer Reviewed
• [Journal Article] Analysis of the complete open reading frame of hepatitis C virus in genotype 2a infection reveals critical sites influencing the response to peginterferon and ribavirin therapy (2011)
  • Author(s): Kadokura M
  • Journal Title: Hepatol Int Volume: 5 Pages: 789-799
  • Peer Reviewed
• [Journal Article] Cancer preventive effect of pegylated interferon α-2b plus ribavirin in a real-life clinical setting in Japan: PERFECT interim analysis (2011)
  • Author(s): Watanabe S
  • Journal Title: Hepatol Res Volume: 41 Issue: 10 Pages: 955
  • DOI: 10.1111/j.1872-034x.2011.00847.x
  • URL: https://pure.teikyo.jp/en/publications/60d0eb69-bb2a-47b1-ba5b-18b006aad977
  • Peer Reviewed
• [Journal Article] Genome-wide association study identified ITPA/DDRGK1 variants reflecting thrombocytopenia in pegylated interferon and ribavirin therapy for chronic hepatitis C (2011)
  • Author(s): Tanaka Y, Sakamoto N, et al.
  • Journal Title: Human Molecular Genetics Volume: 20(17) Issue: 17 Pages: 3507-3516
  • DOI: 10.1093/hmg/ddr249
  • Peer Reviewed
• [Journal Article] HCV genetic elements determining the early response to peginterferon and ribavirin therapy. (2010)
  • Author(s): Enomoto N, Maekawa S.
  • Journal Title: Intervirology Volume: 53(1) Pages: 66-9
  • Peer Reviewed
• [Journal Article] A predictive model of response to peginterferon ribavirin in chronic hepatitis C using classification andregression tree analysis. (2010)
  • Author(s): Kurosaki M, Matsunaga K, Hirayama I, Tanaka T, Sato M, Yasui Y, Tamaki N, Hosokawa T, Ueda K, Tsuchiya K, Nakanishi H, Ikeda H, Itakura J, Takahashi Y, Asahina Y, Higaki M, Enomoto N, Izumi N.
  • Journal Title: Hepatol Res Volume: 40(3) Pages: 251-60
  • Peer Reviewed
• [Journal Article] Mutations in the interferon sensitivity determining region and virological response to combination therapy with pegylated-interferon alpha 2b plus ribavirin in patients with chronic hepatitis C-1b infection. (2010)
  • Author(s): Nakagawa M, Sakamoto N, Ueyama M, Mogushi K, Nagaie S, Itsui Y, Azuma S, Kakinuma S, Tanaka H, Enomoto N, WatanabeM.
  • Journal Title: J Gastroenterol Volume: 45(6) Pages: 656-65
  • NAID: 10027216778
  • Peer Reviewed
• [Journal Article] ITPA gene variant protects against anemia induced by pegylated interferon-αand ribavirin therapy for Japanese patients with chronic hepatitis C. (2010)
  • Author(s): Sakamoto N, Tanaka Y, Nakagawa M, Yatsuhashi H, Nishiguchi S, Enomoto N, AzumaS, Nishimura-Sakurai Y, Kakinuma S, Nishida N, Tokunaga K, Honda M, Ito K, Mizokami M, Watanabe M.
  • Journal Title: Hepatol Res Volume: 40(11) Pages: 1063-1071
  • Peer Reviewed
• [Journal Article] Mutations in the interferon sensitivity determining region and virological response to combination therapy with pegylated-interferon alpha 2b plus ribavirin in patients with chronic hepatitis C-1b infection. (2010)
  • Author(s): Nakagawa M, et al
  • Journal Title: J Gastroenterol. Jan(Epub)
  • Peer Reviewed
• [Journal Article] A predictive model of response to peginterferon ribavirin in chronic hepatitis C using classification and regression tree analysis. (2010)
  • Author(s): Kurosaki M, et al
  • Journal Title: Hepatol Res. 40 Pages: 251-260
  • Peer Reviewed
• [Journal Article] HCV genetic elements determining the early response to peginterferon and ribavirin therapy. (2010)
  • Author(s): Enomoto N, et al
  • Journal Title: Intervirology. 53 Pages: 66-69
  • Peer Reviewed
• [Journal Article] Prolonged treatment with pegylated interferon alpha 2b plus ribavirin improves sustained virological response in chronic hepatitis C genotypel patients with late response in a clinical real-life setting in Janpan. (2010)
  • Author(s): Watanabe S, et al
  • Journal Title: Hepatol Res. 40 Pages: 135-144
  • Peer Reviewed
• [Journal Article] Reproducibility and usability of chronic virus infection model using agent-based simulation ; comparing with a mathematical model. (2010)
  • Author(s): Itakura J, et al
  • Journal Title: Biosystems. 99 Pages: 70-78
  • Peer Reviewed
• [Journal Article] Comparison of HCV-associated gene expression and cell signaling pathways in cells with or without HCV replicon and in replicon-cured cells. (2009)
  • Author(s): Nishimura-Sakurai S, et al
  • Journal Title: J Gastroenterol. Dec(Epub)
  • Peer Reviewed
• [Journal Article] Viral factors influencing the response to the combination therapy of peg interferon plus ribavirin in chronic hepatitis C. (2009)
  • Author(s): Maekawa S, et al
  • Journal Title: J Gastroenterol. 44 Pages: 1009-1015
  • NAID: 10025581619
• [Presentation] 肝炎の進行に関連する肝炎ウイルス遺伝子領域の検索 (2010)
  • Author(s): 三浦美香, ほか
  • Organizer: 第18回浜名湖シンポジウム
  • Place of Presentation: アクトシティ浜松
  • Year and Date: 2010-12-25
• [Presentation] Analysis of the reaponse to pegylated-interferon plus ribavirin therapy in chronic HCV-1b infection using comprehensive information of viral and host factors. (2010)
  • Author(s): Maekawa S, Enomoto N, et al
  • Organizer: EASL(45th Annual meeting of the European association for the study of theliver) WIEN
  • Year and Date: 2010-04-16
• [Presentation] Characterization of protease inhibitor resistance mutations in untreated patients infected with genotype 1b HCV. (2010)
  • Author(s): Shindo H, Maekawa S, Enomoto N, et al
  • Organizer: EASL(45th Annual meeting of the European association for the study of the liver) WIEN
  • Year and Date: 2010-04-15
• [Presentation] Analysis of theearly response and the final outcome topegylated-interferon plus ribavirin therapy inchronic HCV-1b infection using comprehensiveinformation of viral and host factors. (2010)
  • Author(s): Maekawa S, Enomoto N, et al
  • Organizer: 17^<th> International Meeting on Hepatitis C Virus and Related Viruses
  • Place of Presentation: Yokohama
• [Presentation] Extensive analysis of serum cytokines associated to the response in the PEG-IFN+RBV combination therapy in genotype 1b HCV infection. (2010)
  • Author(s): Kazuki Komase, Maekawa S, Enomoto N, et al
  • Organizer: 17^<th> International Meeting on Hepatitis C Virus and Related Viruses
  • Place of Presentation: Yokohama
• [Presentation] Investigation for viral genomic regions associated to hepatocarcinogenesis in hepatitis C. (2010)
  • Author(s): Mika Miura, Maekawa S, Enomoto N, et al
  • Organizer: 17^<th> International Meeting on Hepatitis C Virus and Related Viruses
  • Place of Presentation: Yokohama
• [Presentation] 肝炎の進行と治療感受性を規定するウイルス領域の包括的検討 (2009)
  • Author(s): 前川伸哉
  • Organizer: 第13回日本肝臓学会大会シンポジウム7
  • Place of Presentation: 京都
  • Year and Date: 2009-10-15
• [Presentation] HCVゲノムは抗ウイルス効果を規定する (2009)
  • Author(s): 前川伸哉
  • Organizer: 第45回日本肝臓学会総会ワークショップ
  • Place of Presentation: 神戸
  • Year and Date: 2009-06-04