Analyzing the molecular roles of viral proteins determining the efficacy of anti-viral therapy in hepatitis C virus infection.

• Project/Area Number: 21590837
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: University of Yamanashi
• Principal Investigator: MAEKAWA Shinya 山梨大学, 大学院・医学工学総合研究部, 講師 (70397298)
• Co-Investigator(Kenkyū-buntansha): ENOMOTO Nobuyuki 山梨大学, 大学院・医学工学総合研究部, 教授 (20251530)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: HCV / コア / NS5A / IL28B / インターフェロンλ3 / HCVコア蛋白 / マイクロアレイ解析 / 遺伝子変異 / 薬剤感受性 / 薬剤耐性

Research Abstract

It is known that viral response to the pegylated-interferon plus ribavirin therapy is significantly different depending on the mutational status of core amino acid 70 in chronic hepatitis C virus(HCV) infection. In this study, we tried to clarify the influence of core 70 mutations on the innate immune system as well as viral replication. Moreover, we tried to clarify patients' characteristics depending on the presence of those mutations.

Research Products

• [Journal Article] Inhibition of Hepatitis C Virus Replication and Viral Helicase by Ethyl Acetate Extract of the Marine Feather Star Alloeocomatella polycladia (2012)
  • Author(s): Yamashita A, Abdus K, Furuta A, Matsuda Y, Fujita O, Tani H, Fujita Y, Fujimoto Y, Ikeda M, Kato N, Sakamoto N, Maekawa S, Enomoto N, Nakakoshi M, Tsubuki M, Sekiguchi Y, Tsuneda S, Akimitsu N, Noda N, Tanaka J, and Moriishi K.
  • Journal Title: Mar. Drugs Volume: 10(4) Pages: 744-761
  • Peer Reviewed
• [Journal Article] Inhibition of Hepatitis C Virus Replication and Viral Helicase by Ethyl Acetate Extract of the Marine Feather Star Alloeocomatella polycladia (2012)
  • Author(s): Yamashita A, Maekawa S, et al
  • Journal Title: Mar.Drugs Volume: 10 Issue: 4 Pages: 744-761
  • DOI: 10.3390/md10040744
  • 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, 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] Characterization of naturally occurring protease inhibitor-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] 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, Yamashita A, Kamijo K, Gomi J, Ito M, Maekawa S, Enomoto N, Sakamoto N, Watanabe Y, Arai R, Umeyama H, Honma T, Matsumoto T, Yokoyama S
  • Journal Title: Bioorg Med Chem. Volume: 19(22) Pages: 6892-905
  • 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, Maekawa S, Sueki R, Miura M, Komase K, Shindo H, Amemiya F, Uetake T, Inoue T, Sakamoto M, Nakagawa M, Sakamoto N, Watanabe M, Enomoto N
  • Journal Title: PLoS One. Volume: 6(9)
  • 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, Maekawa S, Sueki R, Miura M, Komase K, Shindo H, Amemiya F, Uetake T, Inoue T, Sakamoto M, Nakagawa M, Sakamoto N, Watanabe M, Enomoto N
  • Journal Title: Hepatol Int. Volume: 5(3) Pages: 789-99
  • Peer Reviewed
• [Journal Article] Pre-treatment prediction of response topegylated-interferon plus ribavirin for chronic hepatitis C using geneticpolymorphism in IL28B and viral factors (2011)
  • Author(s): Kurosaki M, Tanaka Y, Nishida N, Sakamoto N, Enomoto N, Honda M, Sugiyama M, Matsuura K, Sugauchi F, Asahina Y, Nakagawa M, Watanabe M, Sakamoto M, Maekawa S, Sakai A, 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 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] 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, Nakagawa M, Sakamoto N, Watanabe M, et al.
  • Journal Title: Hepatol Int Volume: 5(3) Issue: 3 Pages: 789-799
  • DOI: 10.1007/s12072-011-9267-x
  • Peer Reviewed
• [Journal Article] Pre-treatment prediction of response to pegylated-interferon plus ribavirin for chronic hepatitis C using genetic polymorphism in IL28B and viral factors (2011)
  • Author(s): Kurosaki M, Sakamoto N, Nakagawa M, Watanabe M, et al.
  • Journal Title: J Hepatol Volume: 54 Issue: 3 Pages: 439-448
  • DOI: 10.1016/j.jhep.2010.07.037
  • Peer Reviewed
• [Journal Article] Analysis of the response to pegylated-interferon plus ribavhPin therapy in chronicHCV-1b infection using comprehensive information of viral and host factors. (2011)
  • Author(s): Kadokura M, et al
  • Journal Title: Hepatol Int. Volume: (In press)
  • Peer Reviewed
• [Journal Article] Pre-treatment prediction of response to pegylated-interferon plus ribavirin for chronic hepatitis C using genetic polymorphism in IL28B viral factors. (2011)
  • Author(s): Kurosaki M., et al
  • Journal Title: J Hepatol. Volume: 54 Pages: 439-48
  • 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] Reproducibility and usability of chronic virus infection model using agent-based simulation ; comparing with a mathematical model (2010)
  • Author(s): Itakura J, Kurosaki M, Itakura Y, Maekawa S, Asahina Y, Izumi N, Enomoto N
  • Journal Title: Biosystems Volume: 99(1) Pages: 70-8
  • Peer Reviewed
• [Journal Article] HCV genetic elements determining the early response to peginte rferon and ribavirin therapy. (2010)
  • Author(s): Enomoto N, et al
  • Journal Title: Intervirology. Volume: 53 Pages: 66-9
  • Peer Reviewed
• [Journal Article] Reproducibility and usability of chronic virus infection model using agent-based simulation ; comparing with amathematical model. (2010)
  • Author(s): Itakura J, et al
  • Journal Title: N.Biosystems. Volume: 99 Pages: 70-8
  • 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: 66-9
  • Peer Reviewed
• [Journal Article] Viral factors influencing the response to the combination therapy of peginterferon plus ribavirin in chronic hepatitis C (2009)
  • Author(s): Maekawa S, Enomoto N
  • Journal Title: J Gastroenterol Volume: 44(10) Pages: 1009-15
  • NAID: 10025581619
  • Peer Reviewed
• [Journal Article] DICKKOPF-4 and-2 genes are upregulated in human colorectal cancer (2009)
  • Author(s): Matsui A, Yamaguchi T, Maekawa S, Miyazaki C, Takano S, Uetake T, Inoue T, Otaka M, Otsuka H, Sato T, Yamashita A, Takahashi Y, Enomoto N
  • Journal Title: Cancer Sci Volume: 100(10) Pages: 1923-30
  • NAID: 10027195914
  • Peer Reviewed
• [Journal Article] Two flavonoids extracts from Glycyrrhizae radix inhibit in vitro hepatitis C virus replication (2009)
  • Author(s): Sekine-Osajima Y, Sakamoto N, Nakagawa M, Itsui Y, Tasaka M, Nishimura-Sakurai Y, Chen CH, Suda G, Mishima K, Onuki Y, Yamamoto M, Maekawa S, Enomoto N, Kanai T, Tsuchiya K, Watanabe M
  • Journal Title: Hepatol Res. Volume: 39(1) Pages: 60-9
  • NAID: 10025324061
  • Peer Reviewed
• [Journal Article] Viral factors influencing the response to the combination therapy of peginterferon plus ribavirin in chronic hepatitis C. (2009)
  • Author(s): Maekawa S, et al
  • Journal Title: J Gastroenterol. 44 Pages: 1009-1015
  • NAID: 10025581619
• [Journal Article] Reproducibility and usability of chronic virus infection model using agent-based simulation ; comparing with a mathematical model. (2009)
  • Author(s): Itakura J, et al.
  • Journal Title: N.Biosystems. 99 Pages: 70-78
  • Peer Reviewed
• [Journal Article] DICKKOPF-4 and -2 genes are upregulated in human colorectal cancer. (2009)
  • Author(s): Matsui A, et al.
  • Journal Title: Cancer Sci. 100 Pages: 1923-1930
  • Peer Reviewed
• [Presentation] ウイルスゲノム、およびIL28B SNP解析を用いたHCV肝病態の検討 (2011)
  • Author(s): 前川伸哉
  • Organizer: 第47回日本肝臓学会総会
  • Place of Presentation: 東京
• [Presentation] HCV全長解析によるIL28B SNPと独立して治療効果を規定するウイルス因子の検討 (2011)
  • Author(s): 前川伸哉
  • Organizer: 第15回日本肝臓学会大会
  • Place of Presentation: 福岡
• [Presentation] ウイルスゲノム、およびIL28B SNP解析を用いたHCV肝病態の検討 (2011)
  • Author(s): 前川伸哉
  • Organizer: 第47回日本肝臓学会総会
  • Place of Presentation: ホテルグランパシフィックLE DAIBA(東京都)
• [Presentation] HCV全長解析によるIL28B SNPと独立して治療効果を規定するウイルス因子の検討 (2011)
  • Author(s): 前川伸哉
  • Organizer: 第15回日本肝臓学会大会
  • Place of Presentation: 福岡国際センター/福岡国際会議場(福岡県)
• [Presentation] Analysis of the response to pegylated-interferon plus ribavirin therapy in chronicHCV-1b infection using comprehensive information of viral and host factors (2010)
  • Author(s): Maekawa S, et al
  • Organizer: 45th annual meeting of the European Association for the Study of the Liver(EASL2010)
  • Place of Presentation: Vienna, Austria
• [Presentation] Characterization of protease inhibitor resistance mutations in untreated patients infected with genotype 1b hepatitis c virus (2010)
  • Author(s): Shindo H, Maekawa S, et al
  • Organizer: 45th annual meeting of the European Association for the Study of the Liver(EASL2010)
  • Place of Presentation: Vienna, Austria
• [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): Komase K, Maekawa S, et al
  • Organizer: 17th International meeting on hepatitis C virus and related viruses(HCV2010)
  • Place of Presentation: Yokohama, Japan
• [Presentation] Characterization of Protease Inhibitor Resistance Mutations in Untreated Patients Infected with Genotype 1b Hepatitis C Virus (2010)
  • Author(s): Shindo H, Maekawa S, et al
  • Organizer: 17th International meeting on hepatitis C virus and related viruses(HCV2010)
  • Place of Presentation: Yokohama, Japan
• [Presentation] Investigation for viral genomic regions associated to hepatocarcinogenesis in hepatitis C (2010)
  • Author(s): Miura M, Maekawa S, et al
  • Organizer: 17th International meeting on hepatitis C virus and related viruses(HCV2010)
  • Place of Presentation: Yokohama, Japan
• [Presentation] Analysis of the response to pegylated-interferon plus ribavirin therapy in chronicHCV-1b infection using comprehensive information of viral and host factors. (2010)
  • Author(s): Maekawa S, et al.
  • Organizer: 45th annual meeting of the European Association for the Study of the Liver(EASL2010).
  • Place of Presentation: Vienna, Austria.
• [Presentation] Characterization of protease inhibitor resistance mutations in untreated patients infected with genotype 1b hepatitis c virus. (2010)
  • Author(s): Shindo H, et al.
  • Organizer: 45th annual meeting of the European Association for the Study of the Liver(EASL2010).
  • Place of Presentation: Vienna, Austria.
• [Presentation] Extensive analysis of Serum Cytokines Associated to The Response in The PEG-IFN+RBVCombination Therapy in Genotype 1b HCV Infection. (2010)
  • Author(s): Komase K, et al
  • Organizer: 17th Interational meeting on hepatitis C virus and related viruses(HCV2010).
  • Place of Presentation: Yokohama, Japan.
• [Presentation] Characterization of Protease Inhibitor Resistance Mutations in Untreated Patients Infected with Genotype 1b Hepatitis C Virus. (2010)
  • Author(s): Shindo H, et a1.
  • Organizer: 17th International meeting on hepatitis C virus and related viruses(HCV2010).
  • Place of Presentation: Yokohama, Japan.
• [Presentation] Investigation for viral genomic regions associated to hepatocarcinogenesis in hepatitis C. (2010)
  • Author(s): Miura M, et al.
  • Organizer: 17th International meeting on hepatitis C virus and related viruses(HCV2010).
  • Place of Presentation: Yokohama, Japan.
• [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
  • Place of Presentation: 京都
  • Year and Date: 2009-10-15
• [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