Mechanism of Neutralization using Infectious Hepatitis C Chimeric Viruses

• Project/Area Number: 20590757
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Yamagata University
• Principal Investigator: WATANABE Hisayoshi 山形大学, 医学部, 講師 (00332536)
• Co-Investigator(Kenkyū-buntansha): SHAO Li 山形大学, 医学部, 助教 (80344787)
• Co-Investigator(Renkei-kenkyūsha): ISHII Rika 山形大学, 医学部, 助教 (60466612)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: HCV / ワクチン / 中和抗体 / C型肝炎

Research Abstract

Neutralizing antibody (NAb) is thought to play an important role in HCV infection. Detailed analysis of HCV NAb titer using newly developed cell culture system was performed. The level of NAb was low in the early phase of infection, suggested the cytotoxic immune response was a major role. While, the titer of NAb was decreased because of the sequence of neutralizing epitope was changed during the chronic phase. These results suggest the mechanism why HCV can be infected persistently.

Research Products

• [Journal Article] (99m) Tc-GSA SPECT analysis was clinically useful to evaluate the effect of interferon in a patient with interferon non-responsive chronic hepatitis C (2011)
  • Author(s): Ishii R, Togashi H, Iwaba A, Sato C, Haga H, Sanjo M, Okumoto K, Nishise Y, Ito JI, Watanabe H, Saito K, Okada A, Takahashi K, Saito T, Kawata S
  • Journal Title: Ann Nucl Med Pages: 520-523
  • NAID: 10029525687
  • Peer Reviewed
• [Journal Article] Potential therapeutic application of intravenous autologous bone marrow infusion in patients with alcoholic liver cirrhosis (2011)
  • Author(s): Saito T, Okumoto K, Haga H, Nishise Y, Ishii R, Sato C, Watanabe H, Okada A, Ikeda M, Togashi H, Ishikawa T, Terai S, Sakaida I, Kawata S
  • Journal Title: Stem Cells Dev Pages: 1503-1510
  • Peer Reviewed
• [Journal Article] Sequence heterogeneity of NS5A and core proteins of hepatitis C virus and virological responses to pegylated-interferon/ribavirin combination therapy (2011)
  • Author(s): El-Shamy A, Shoji I, Saito T, Watanabe H, Ide YH, Deng L, Kawata S, Hotta H
  • Journal Title: Microbiol Immunol Pages: 418-426
  • NAID: 10031121486
  • Peer Reviewed
• [Journal Article] Serum metabolomics reveals γ-glutamyl dispeptides as biomarkers for discrimination among different forms of liver disease (2011)
  • Author(s): Soga T, Sugimoto M, Honma M, Mori M, Igarashi K, Kashikura K, Ikeda S, Hirayama A, Yamamoto T, Yoshida H, Otsuka M, Tsuji S, Yatomi Y, Sakuragawa T, Watanabe H, Nihei K, Saito T, Kawata S, Suzuki H, Tomita M, Suematsu M
  • Journal Title: J Hepatol Pages: 896-965
  • Peer Reviewed
• [Journal Article] Enhanced expression of fibroblast growth factor 2 in bone marrow cells and its potential role in the differentiation of hepatic epithelial stem-like cells into the hepatocyte lineage (2010)
  • Author(s): Haga H, Saito T, Okumoto K, Ugajin S, Sato C, Ishii R, Nishise Y, Ito J, Watanabe H, Saito K, Togashi H, Kawata S
  • Journal Title: Cell Tissue Res Volume: 343 Pages: 371-378
  • Peer Reviewed
• [Journal Article] Secondary structure of the amino-terminal region of HCV NS3 and virological response to pegylated interferon plus ribavirin therapy for chronic hepatitis C (2010)
  • Author(s): Sanjo M, Saito T, Nishise Y, Haga H, Okumoto K, Ito J, Watanabe H, Saito K, Togashi H, Fukuda K, Imai Y, El Shamy A, Deng L, Shoji I, Hotta H, Kawata S
  • Journal Title: J Med Virol Volume: 82 Pages: 1364-1370
  • Peer Reviewed
• [Journal Article] Relationship between alcohol consumption and serum adiponection levels : the Takahata study-a cross-sectional study of a healthy Japanese population (2010)
  • Author(s): Nishise Y, Saito T, Makino N, Okumoto K, Ito JI, Watanabe H, Saito K, Togashi H, Ikeda C, Kubota I, Daimon M, Kato T, Fukao A, Kawata S
  • Journal Title: J Clin Endocrinol Metab Volume: 95 Pages: 3828-3835
  • Peer Reviewed
• [Journal Article] Expression of the RNA-binding protein Musashi1 in adult liver stem-like cells (2010)
  • Author(s): Hattori E, Shu HJ, Saito T, Okumoto K, Haga H, Yokozawa J, Ito J, Watanabe H, Saito K, Togashi H, Kawata S
  • Journal Title: Hepatol Res Volume: 40 Pages: 432-437
  • NAID: 10027291781
  • Peer Reviewed
• [Journal Article] Clearance of hepatitis C in chimpanzees is associated with intrahepatic T-cell perforin expression during late acute phase (2010)
  • Author(s): Watanabe H, Wells F, Major ME
  • Journal Title: J Viral Hepatitis Volume: 17 Pages: 245-253
  • Peer Reviewed
• [Journal Article] Relationship between alcohol consumption and serum adiponection levels : the Takahata study- a cross-sectional study of a healthy Japanese population (2010)
  • Author(s): Nishise Y, Saito T, Watanabe H, et al
  • Journal Title: J Clin Endocrinol Metab Volume: 95 Pages: 3828-3835
  • Peer Reviewed
• [Journal Article] Impact of metabolic syndrome on elevated serum alanine aminotransferase levels in the Japanese population (2009)
  • Author(s): Saito T, Nishise Y, Makino N, Haga H, Ishii R, Okumoto K, Ito JI, Watanabe H, Saito K, Takeda H, Togashi H, Kubota I, Daimon M, Kato T, Kawata S
  • Journal Title: Metabolism Volume: 58 Pages: 1067-1075
  • Peer Reviewed
• [Journal Article] Depletion of interfering antibodies in chronic hepatitis C patients and vaccinated chimpanzees reveals broad cross-genotype neutralizing activity (2009)
  • Author(s): Zhang P, Zhong L, Struble EB, Watanabe H, Kachko A, Mihalik K, Virata-Theimer ML, Alter HJ, Feinstone S, Major ME
  • Journal Title: Proc Natl Acad Sci USA Volume: 106(18) Pages: 7537-7541
  • Peer Reviewed
• [Journal Article] T-cell vaccines that elicit effective immune responses against HCV in chimpanzees may create greater immune pressure for viral mutation (2009)
  • Author(s): Zubkova I, Choi YH, Chang E, Pirollo K, Uern T, Watanabe H, Wells F, Kachko A, Krawczynski K, Major ME
  • Journal Title: Vaccine Volume: 27 Pages: 2594-2602
  • Peer Reviewed
• [Journal Article] T-cell vaccines that elicit effective immune responses against HCV in chimpanzees may create greater immune pressure for viral mutation. (2009)
  • Author(s): Zubkova I, Choi Y.H., Watanabe H, et.al
  • Journal Title: Vaccine 27 Pages: 2594-2602
  • Peer Reviewed
• [Journal Article] Depletion of interfering antibodies in chronic hepatitis C patients and vaccinated chimpanzees reveals broad cross-genotype neutralizing activity. (2009)
  • Author(s): Zhang P, Zhong L.Struble EB, Watanabe H, et.al
  • Journal Title: Proc Natl Acad Sci USA 106 Pages: 7537-7541
  • Peer Reviewed
• [Presentation] Incidence of hepatocellular carcinoma after achieving sustained virological response to interferon therapy for chronic hepatitis C (2010)
  • Author(s): Watanabe H, Saito T, Ishii R, Sato C, Haga H, Sanjo M, Okumoto K, Nishise Y, Ito J, Saito K, Kawata S
  • Organizer: The 61th Annual Meeting of the American Association for the Study of Liver Diseases
  • Place of Presentation: Boston,USA
  • Year and Date: 2010-11-03
• [Presentation] Clearance of hepatitis C virus in chimpanzees is associated with intrahepatic perforin expression during the late acute phase (2010)
  • Author(s): Watanabe H, Wells F, Saito T, Sato C, Ishii R, Haga H, Sanjo M, Okumoto K, Nishise Y, Ito J, Saito K, Kawata S, Major ME
  • Organizer: 18th United European Gastroenterology Week
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2010-10-26
• [Presentation] B型肝炎ジェノタイプB型高浸淫地域における急性B型肝炎の実態 (2010)
  • Author(s): 渡辺久剛, 斎藤貴史, 西瀬雄子, 佐藤智佳子, 石井里佳, 芳賀弘明, 三條麻衣, 奥本和夫, 伊藤純一, 斉藤孝治, 冨樫整, 新澤陽英, 河田純男
  • Organizer: 第14回日本肝臓学会大会
  • Place of Presentation: 横浜市パシフィコ横浜
  • Year and Date: 2010-10-13
• [Presentation] HCVコホート研究による持続感染者の自然経過 (2010)
  • Author(s): 渡辺久剛, 斎藤貴史, 西瀬雄子, 邵力, 佐藤智佳子, 石井里佳, 芳賀弘明, 三條麻衣, 奥本和夫, 伊藤純一, 斉藤孝治, 石橋正道, 冨樫整, 新澤陽英, 河田純男
  • Organizer: 第46回日本肝臓学会総会サテライトシンポジウム「HCV感染のnatural courseを探る:わが国におけるコホート研究」
  • Place of Presentation: 山形市山形テルサ
  • Year and Date: 2010-05-29
• [Presentation] HCVコホートにおけるウイルス自然治癒および肝発癌の検討 (2010)
  • Author(s): 渡辺久剛, 斎藤貴史, 西瀬雄子, 佐藤智佳子, 石井里佳, 芳賀弘明, 三條麻衣, 奥本和夫, 伊藤純一, 斉藤孝治, 冨樫整, 新澤陽英, 河田純男
  • Organizer: 第46回日本肝臓学会総会
  • Place of Presentation: 山形市ホテルメトロポリタン山形
  • Year and Date: 2010-05-27
• [Presentation] Clearance of hepatitis C virus in chimpanzees is associated with intrahepatic perforin expression during the late acute phase (2010)
  • Author(s): Watanabe H, et al
  • Organizer: 18th United European Gastroenterology Week
  • Place of Presentation: スペイン、バルセロナ
• [Presentation] Incidence of hepatocellular carcinoma after achieving sustained virological response to interferon therapy for chronic hepatitis C (2010)
  • Author(s): Watanabe H, et al
  • Organizer: 61th Annual Meeting of the American Association for the Study of Liver Diseases
  • Place of Presentation: 米国、ボストン
• [Presentation] HCVコホートにおけるウイルス自然治癒および肝発癌の検討 (2010)
  • Author(s): 渡辺久剛, ほか
  • Organizer: 第46回日本肝臓学会総会
  • Place of Presentation: 山形県山形市ホテルメトロポリタン山形
• [Presentation] B型肝炎ジェノタイプB型高浸淫地域における急性B型肝炎の実態 (2010)
  • Author(s): 渡辺久剛, ほか
  • Organizer: 第14回日本肝臓学会大会
  • Place of Presentation: 神奈川県横浜市パシフィコ横浜
• [Presentation] Natural Clearance of Hepatitis C Virus (HCV) RNA in Chronic HCV Carriers : A Long-Term Cohort Study in an Endemic Area of HCV Infection in Japan (2009)
  • Author(s): Watanabe H, Saito T, Nishise Y, Sasaki Y, Sato C, Ishii R, Haga H, Sanjo M, Okumoto K, Ito J, Saito K, Shinzawa H, Kawata S
  • Organizer: 60th Annual Meeting of the American Association for the Study of Liver Diseases
  • Place of Presentation: Boston, USA
  • Year and Date: 2009-11-03
• [Presentation] Natural Clearance of Hepatitis C Virus(HCV)RNA in Chronic HCV Carriers : A Long-Term Cohort Study in an Endemic Area of HCV Infection in Japan. A (2009)
  • Author(s): 渡辺久剛, et al.
  • Organizer: 60th Annual Meeting of the American Association for the Study of Liver Diseases
  • Place of Presentation: 米国、ボストン
  • Year and Date: 2009-11-02
• [Presentation] Real-time PCR法を用いたHCV持続感染者におけるウイルス自然陰性化の検討 (2009)
  • Author(s): 渡辺久剛, 斎藤貴史, 西瀬雄子, 佐藤智佳子, 宇賀神智, 石井里佳, 芳賀弘明, 三條麻衣, 奥本和夫, 伊藤純一, 斉藤孝治, 冨樫整, 新澤陽英, 河田純男
  • Organizer: 第45回日本肝臓学会総会
  • Place of Presentation: 神戸市神戸ポートピアホテル
  • Year and Date: 2009-06-04
• [Presentation] Real-time PCR法を用いたHCV持続感染者におけるウイルス自然陰性化の検討 (2009)
  • Author(s): 渡辺久剛
  • Organizer: 第45回日本肝臓学会総会
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2009-06-04
• [Presentation] A Long-Term Population-Based Cohort Study in an Endemic Area of Hepatitis C Virus in Japan : Spontaneous Elimination of Serum HCV RNA Detected by the Real-Time PCR System (2009)
  • Author(s): Watanabe H, Saito T, Shao L, Nishise Y, Ishii R, Haga H, Okumoto K, Ito J, Saito K, Shinzawa H, Kawata S
  • Organizer: 13th International Symposium on Viral Hepatitis and Liver Disease
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2009-03-18
• [Presentation] 1a/2a chimera HCV培養細胞感染系を用いたHCV中和抗体レベルの解析 (2008)
  • Author(s): 渡辺久剛, 斉藤貴史, 河田純男
  • Organizer: シンポジウム「C型ウイルス肝炎治療の新潮流」第44回日本肝臓学会総会
  • Place of Presentation: 松山市愛媛県県民文化会館
  • Year and Date: 2008-06-05
• [Presentation] 1a/2a chimera HCV培養細胞感染系を用いた中和抗体レベルの解析 (2008)
  • Author(s): 渡辺久剛
  • Organizer: 第44回日本肝臓学会総会
  • Place of Presentation: 愛媛県松山市
  • Year and Date: 2008-06-04
• [Book] HCVコホート研究による持続感染者の自然経過.HCV感染のnatural courseを探る:わが国におけるコホート研究(河田純男監修、佐田通夫・新沢陽英・斎藤貴史編) (2011)
  • Author(s): 渡辺久剛, 斎藤貴史, 西瀬雄子, 邵力, 佐藤智佳子, 石井里佳, 芳賀弘明, 奥本和夫, 斎藤孝治, 冨樫整, 新沢陽英, 河田純男
  • Publisher: 山形大学出版
• [Book] HCVコホート研究による持続感染者の自然経過.HCV感染のnatural courseを探る:わが国におけるコホート研究(河田純男監修、佐田通夫・新沢陽英・斎藤貴史編) (2011)
  • Author(s): 渡辺久剛, ほか
  • Publisher: 山形大学出版
• [Book] 分子標的薬治療における消化器症状対策.分子標的薬トータルマネージメントYURCCパッケージver.1.2(冨田善彦編) (2010)
  • Author(s): 渡辺久剛
  • Publisher: リッチヒルメディカル
• [Book] 慢性肝炎.ハリソン内科学第3版(福井次矢、黒川清編) (2009)
  • Author(s): 渡辺久剛, 河田純男
  • Publisher: メディカル・サイエンス・インターナショナル
• [Book] HCVキャリアからのHCV RNA自然消失はあるのか?肝臓病診療こんなときどうするQ & A(河田純男、佐々木裕編) (2009)
  • Author(s): 渡辺久剛, 河田純男
  • Publisher: 中外医学社
• [Book] PegIFN+リバビリン療法の治療効果はウイルス学的にどこまで予測できるか?肝臓病診療こんなときどうするQ & A(河田純男、佐々木裕編) (2009)
  • Author(s): 齋藤貴史, 渡辺久剛, 河田純男
  • Publisher: 中外医学社
• [Book] 当科における肝硬変の成因別実態.肝硬変の成因別実態(青柳豊、他編) (2008)
  • Author(s): 宇賀神智, 奥本和夫, 斎藤貴史, 佐藤智佳子, 芳賀弘明, 石井里佳, 鈴木明彦, 三條麻衣, 西瀬雄子, 伊藤純一, 菅原一彦, 渡辺久剛, 斎藤孝治, 冨樫整, 河田純男
  • Publisher: 中外医学社
• [Book] 肝硬変.肝臓病のすべて(与芝真彰編) (2008)
  • Author(s): 渡辺久剛, 河田純男
  • Publisher: 日本評論社