The study of development of the new therapeutic target for the hepatitis C virus through the influence of the lipid metabolism

• Project/Area Number: 22590743
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Yokohama City University
• Principal Investigator: SAITO Satoru 横浜市立大学, 医学部, 准教授 (00275041)
• Co-Investigator(Kenkyū-buntansha): NAKAJIMA Atsushi 横浜市立大学, 附属病院, 教授 (30326037) ; KIRIKOSHI Hiroyuki 横浜市立大学, 附属病院, 助教 (80347294)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: ウイルス / 肝炎 / 内科 / 感染症 / 感染

Research Abstract

The hepatitis C virus (HCV) is affecting a host's lipid metabolism, and there isa possibility of raising the efficiency of infection and multiplicationby HCV protein. We showed that especially HCV protein controlled the hepatic triglyceride lipase (HTGL) which metabolizes very-low density lipoprotein (VLDL). This phenomenon was similarly approved in a host's liver. In conclusion,the substance, which could increase theHTGLexpression,could be anew therapeutictarget forHCV.

Research Products

• [Journal Article] Unfolded Protein Response pathways regulate Hepatitis C Virus replication via modulation of Autophagy (2013)
  • Author(s): Shinohara,Y, Imajo K, Yoneda M, Tomeno W, Ogawa Y, Kirikoshi H, Funakoshi K, Ikeda M, Kato N, Nakajima A, Saito S
  • Journal Title: Biochem Biophys Res Commun
  • Peer Reviewed
• [Journal Article] Hepatic triglyceride lipaseplays an essential role in changing the lipid metabolism in genotype 1b hepatitis C virus replicon cells and hepatitis C patients (2013)
  • Author(s): ShinoharaY, Imajo K, Yoned M, Tomeno W, Ogawa Y, Fujita K, Kirikoshi H, Takahashi J, Funakoshi K, Ikeda M, Kato N, Nakajima A, Saito S
  • Journal Title: Hepatol Res Volume: 43 Issue: 11 Pages: 1190-1198
  • DOI: 10.1111/hepr.12072
  • Peer Reviewed
• [Journal Article] Hepatic triglyceride lipase plays an essential role in changingthe lipid metabolism in genotype 1b hepatitis C virus replicon cells and hepatitis C patients. (2013)
  • Author(s): ShinoharaYoshiyasu
  • Journal Title: Hepatol Res. Volume: in press
  • Peer Reviewed
• [Journal Article] Unfolded Protein Response pathways regulate Hepatitis C Virus replication via modulation of Autophagy (2013)
  • Author(s): ShinoharaYoshiyasu
  • Journal Title: Biochem Biophys Res Commun Volume: in press
  • Peer Reviewed
• [Journal Article] Association between lipoprotein subfraction profile and the response to hepatitis C treatment in Japanese patients with genotype 1b (2010)
  • Author(s): Mawatari H, Yoneda M, Fujita K,Nozaki Y, Shinohara Y, Sasaki H, Iida H, Takahashi H, Inamori M, Abe Y, Kobayashi N, Kubota K, Kirikoshi H, Nakajima A, Saito S
  • Journal Title: J Viral Hepat Volume: 17(4) Pages: 274-279
  • Peer Reviewed
• [Journal Article] Association between phospholipids and free cholesterol in high-density lipoprotein andthe response to hepatitis C treatment in Japanese with genotype 1b (2010)
  • Author(s): Mawatari H, Yoneda M, Fujita K, Nozaki Y, Shinohara Y, Sasaki H, Iida H, Takahashi H, Inamori M, Abe Y, Kobayashi N, Kubota K, Kirikoshi H, Nakajima A, Saito S
  • Journal Title: J Viral Hepat Volume: 17(12) Pages: 859-865
  • Peer Reviewed
• [Journal Article] Association between lipoprotein subfraction profile and the response to hepatitis C treatment in Japanese patients with genotype 1b (2010)
  • Author(s): Mawatari Hironori
  • Journal Title: J Viral Hepat Volume: 17 Pages: 274-279
  • Peer Reviewed
• [Presentation] Tu1037 Dipeptidyl Peptidase-4 (Dpp-4) Inhibitor (Sitagliptin) as a Novel Treatment Agent for Nonalcoholic Fatty Liver Disease Patients With Type 2 Diabetes Mellitus. (2012)
  • Author(s): Tomeno Wataru
  • Organizer: DIGESTIVE DISEASE WEEK 2012
  • Place of Presentation: San Diego, USA
• [Presentation] Evaluation of the Liver Fibrosis Index (LF Index) calculated by using real-time tissue elastographyfor the noninvasive assessment of liver fibrosis (2012)
  • Author(s): Tomeno Wataru
  • Organizer: 19th INTERNATIONAL SYMPOSIUM ON HEPATITIS C VIRUS AND RELATED VIRUSES
  • Place of Presentation: Venice, Italy
• [Presentation] HCVレプリコン細胞におけるVLDL,LDLrecepterの検討 (2011)
  • Author(s): 篠原義康, 斉藤聡
  • Organizer: 第23回日本肝臓学会西部会
  • Place of Presentation: 岡山コンベンションセンター(岡山)
  • Year and Date: 2011-12-10
• [Presentation] Autophagy regulates Hepatitis C Virus replication (2011)
  • Author(s): Shinohara Y, Saito S
  • Organizer: THE 62ND ANNUAL MEETING OF THE AMERICAN ASSOCIATION OF THE STUDY OF THE LIVER DISEASES
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2011-11-08
• [Presentation] HCV proteins are involved in selective autophagy (2011)
  • Author(s): Shinohara Y, Saito S
  • Organizer: THE 62ND ANNUAL MEETING OF THE AMERICAN ASSOCIATION OF THE STUDY OF THE LIVER DISEASES
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2011-11-08
• [Presentation] Breakthough of acute hepatitis C while on interferon is as sociated with changes in diversity in hepatitis C virus non structural proteins but not changes in responsiveness (2011)
  • Author(s): Hara Koji, Saito S
  • Organizer: THE 62ND ANNUAL MEETING OF THE AMERICAN ASSOCIATION OF THE STUDY OF THE LIVER DISEASES
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2011-11-08
• [Presentation] Autophagy regulates Hepatitis C Virus replication (2011)
  • Author(s): Shinohara Y, Fujita K, Imajo K, Mawatari H, Yoneda M, Shibata A, Kirikoshi H, Funakoshi K, Ikeda M, Kato N, Maeda S, Nakajima A,Saito S
  • Organizer: The62ndAASLD
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2011-11-07
• [Presentation] HCV proteins are involved in selective autophagy (2011)
  • Author(s): Shinohara Y, Fujita K, Imajo K, Mawatari H, Yoneda M, Shibata A, Kirikoshi H, Funakoshi K, Ikeda M, Kato N, Maeda S, Nakajima A,Saito S
  • Organizer: The62ndAASLD
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2011-11-07
• [Presentation] Hepatitis C Virus induces aggregation of p62 (2011)
  • Author(s): 篠原義康,加藤真吾, 池田正徳, 加藤宣之, 前田慎, 中島淳, 斉藤聡
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2011-10-04
• [Presentation] Hepatitis C Virus induces aggregation of p62 (2011)
  • Author(s): 篠原義康, 斉藤聡
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋)
  • Year and Date: 2011-10-04
• [Presentation] Hepatitis C Virus regulates p62 metabolism (2011)
  • Author(s): Shinohara Y, Fujita K, Imajo K, Mawatari H, Yoneda M, Shibata A, Kirikoshi H, Funakoshi K, Ikeda M, Kato N, Maeda S, Nakajima A, Saitou S
  • Organizer: International Union of Microbiological Societies Sapporo, Japan
  • Place of Presentation: Sapporo Convention Center(hokkaido)
  • Year and Date: 2011-09-15
• [Presentation] Hepatitis C Virus regulates p62 metabolism (2011)
  • Author(s): 篠原義康, 斉藤聡
  • Organizer: International Union of Microbiological Societies 2011 Congress
  • Place of Presentation: 札幌コンベンションセンター(札幌)
  • Year and Date: 2011-09-15
• [Presentation] HCVレプリコン細胞におけるVLDL, LDLrecepterの検討 (2011)
  • Author(s): 篠原義康, 馬渡弘典, 藤田浩司, 米田正人, 今城健人, 芝田渉,桐越博之, 船越健悟, 池田正徳, 加藤宣之, 前田慎, 中島淳, 斉藤聡
  • Organizer: 第23回日本肝臓学会西部会
  • Place of Presentation: 岡山プラザホテル
  • Year and Date: 2011-06-12
• [Presentation] C型慢性肝炎における肝線維化とCETP活性の関係 (2011)
  • Author(s): 馬渡弘典, 斉藤聡
  • Organizer: 第47回日本肝臓学会総会
  • Place of Presentation: グランパシフィックLE DAIBA(東京)
  • Year and Date: 2011-06-02
• [Presentation] HCVレプリコン細胞を用いたER stressを介した細胞死の検討およびHCV複製増殖におけるオートファジーの役割 (2010)
  • Author(s): 篠原義康, 藤田浩司, 米田正人, 野崎雄一, 今城健人, 鈴木香峰理, 馬渡弘典, 桐越博之, 船越健悟, 池田正徳, 加藤宣之, 前田慎, 中島淳, 斉藤聡
  • Organizer: 第33回日本分子生物学会1P-1047 兵庫
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2010-12-07
• [Presentation] HCV感染におけるERストレスを介した細胞死の検討 (2010)
  • Author(s): 篠原義康
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 神戸・神戸ポートアイランド
  • Year and Date: 2010-12-07
• [Presentation] HCVレプリコン細胞を用いたリポ蛋白代謝の解析 (2010)
  • Author(s): 篠原義康, 藤田浩司, 米田正人, 野崎雄一, 今城健人, 鈴木香峰理, 馬渡弘典, 桐越博之, 船越健悟, 池田正徳, 加藤宣之, 前田慎, 中島淳, 斉藤聡
  • Organizer: 肝臓学会東部会O-135 東京
  • Place of Presentation: 京王プラザホテル
  • Year and Date: 2010-12-03
• [Presentation] Hepatic triglyceride lipase may play important role to change the lipoprotein profiles in the HCV replicon system (2010)
  • Author(s): ShinoharaY, FujitaK, NozakiY, ImajoK, MawatariH, YonedaM, KirikoshiH, FunakoshiK, IkedaM, KatoN, MaedaS, NakajimaA, SaitouS
  • Organizer: American Association for the Study of Liver Diseases1048
  • Place of Presentation: Boston, USA
  • Year and Date: 2010-11-07
• [Presentation] The ER stress caused by hepatitis C virus in replicon cells was reversed by interferon treatment (2010)
  • Author(s): ShinoharaY, FujitaK, NozakiY, ImajoK, MawatariH, YonedaM,KirikoshiH, FunakoshiK, IkedaM, KatoN, MaedaS, NakajimaA, SaitouS
  • Organizer: American Association for the Study of Liver Diseases877
  • Place of Presentation: Boston, USA
  • Year and Date: 2010-11-07
• [Presentation] HCVレプリコン細胞におけるリポ蛋白代謝の解析. 第58回ウイルス学会01-5-15 (2010)
  • Author(s): 篠原義康, 藤田浩司, 米田正人, 野崎雄一, 今城健人, 鈴木香峰理, 馬渡弘典, 桐越博之, 船越健悟, 池田正徳, 加藤宣之, 前田慎, 中島淳, 斉藤聡
  • Organizer: 第58回ウイルス学会01-5-15
  • Place of Presentation: 徳島,あわぎんホール
  • Year and Date: 2010-11-07
• [Presentation] HCV感染におけるリポ蛋白代謝の解析 (2010)
  • Author(s): 篠原義康
  • Organizer: 第58回日本ウイルス学会学術集会
  • Place of Presentation: 徳島・あわぎんホール
  • Year and Date: 2010-11-07
• [Presentation] THE ER STRESS CAUSED BY HEPATITIS C VIRUS IN REPL1 CON CELLS WAS REVERSED BY INTERFERON TREATMENT (2010)
  • Author(s): Shinohara Yoshiyasu
  • Organizer: 61^<th> Annual Meeting of the American Association for the Study of Liver Diseases (AASLD)
  • Place of Presentation: Boston, USA
  • Year and Date: 2010-10-31
• [Presentation] HEPATIC TRIGLYCERIDE LIPASE MAY PLAY IMPORTANT ROLE TO CHANGE THE LIPOPROTEIN PROFILES IN THE HCV REPLICON SYSTEM (2010)
  • Author(s): Shinohara Yoshiyasu
  • Organizer: 61^<th> Annual Meeting of the American Association for the Study of Liver Diseases (AASLD)
  • Place of Presentation: Boston, USA
  • Year and Date: 2010-10-31
• [Presentation] Clearance of the Hepatitis C virus replicon by interferon-alpha treatment restored the signal pathway involving JNK (2010)
  • Author(s): ShinoharaY, FujitaK, NozakiY, ImajoK, MawatariH, YonedaM,KirikoshiH, FunakoshiK, IkedaM, KatoN, MaedaS, NakajimaA,SaitoS
  • Organizer: 17th International Meeting on Hepatitis C Virus and Related Viruses
  • Place of Presentation: Japan,Pacifico Yokohama(kanagawa)
  • Year and Date: 2010-09-11
• [Presentation] Hepatitis C Virus infection changes the lipoprotein profiles in the replicon system (2010)
  • Author(s): ShinoharaY, FujitaK, NozakiY, ImajoK, MawatariH, YonedaM, KirikoshiH, FunakoshiK, IkedaM, KatoN, MaedaS, NakajimaA, SaitoS
  • Organizer: 17th International Meeting on Hepatitis C Virus and Related Viruses
  • Place of Presentation: Japan, Pacifico Yokohama(kanagawa)
  • Year and Date: 2010-09-11
• [Presentation] Clearance of the Hepatitis C virus replicon by interferon-alpha treatment restored the signal pathway involving JNK (2010)
  • Author(s): Shinohara Yoshiyasu
  • Organizer: 17th International Meeting on Hepatitis C Virus and Related Viruses
  • Place of Presentation: 横浜・パシフィコ横浜
  • Year and Date: 2010-09-11
• [Presentation] Hepatitis C Virus infection changes the lipoprotein profiles in the replicon system (2010)
  • Author(s): Shinohara Yoshiyasu
  • Organizer: 17th International Meeting on Hepatitis C Virus and Related Viruses
  • Place of Presentation: 横浜・パシフィコ横浜
  • Year and Date: 2010-09-11
• [Presentation] Hepatitis C virus遺伝子型1bの脂質代謝関連遺伝子の発現に及ぼす影響 (2010)
  • Author(s): 篠原義康
  • Organizer: 第46回日本肝臓学会総会
  • Place of Presentation: 山形・山形国際ホテル 他
  • Year and Date: 2010-05-28
• [Presentation] 培養細胞におけるHepatitis C virus遺伝子型1bの脂質代謝関連遺伝子の発現に及ぼす影響 (2010)
  • Author(s): 篠原義康,野崎雄一,藤田浩司,米田正人,馬渡弘典,桐越博之,船越健悟,中島淳,斉藤聡
  • Organizer: 第46回日本肝臓学会総会
  • Place of Presentation: 山形国際ホテル
  • Year and Date: 2010-05-27
• [Presentation] HDL-free cholesterolとC型慢性肝炎(genotype1・抗ウイルス量)に対する治療抵抗性との関係 (2010)
  • Author(s): 馬渡弘典
  • Organizer: 第46回日本肝臓学会総会
  • Place of Presentation: 山形・山形国際ホテル 他
  • Year and Date: 2010-05-27
• [Presentation] HDL-free cholesterol is an independent clinical marker of the resistance to hepatitis C treatment. (2010)
  • Author(s): Mawatari Hironori
  • Organizer: DIGESTIVE DISEASE WEEK 2010
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2010-05-04