Controlling HCV replication by targeting intracellular signaling

• Project/Area Number: 21590843
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: 独立行政法人国立病院機構大阪医療センター(臨床研究センター) (2011); Osaka University (2009-2010)
• Principal Investigator: ISHIDA Hisashi 独立行政法人国立病院機構大阪医療センター(臨床研究センター), 研究員 (00506230)
• Co-Investigator(Kenkyū-buntansha): TAKEHARA Tetsuo 大阪大学, 大学院・医学系・研究科, 教授 (70335355)
• 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: C型肝炎ウイルス / BCAA / ウイルス粒子形成 / mTOR / マイクロRNA / PI3キナーゼ

Research Abstract

In this study, we investigated factors affecting intracellular signaling which could control HCV replication. Among microRNAs which were regulated by HCV infection, miR192/miR-215 and miR-491 were identified as the factors which could regulate HCV replication. miR-491 was demonstrated to suppress PI3 kinase/Akt pathway, responsible for HCV augmentation. Branched-chain amino acids could suppress HCV RNA replication whereas enhance HCV particle formation, which suggested some signaling regulated by BCAA may be involved in controlling HCV replication.

Research Products

• [Journal Article] Alterations in microRNA expression profile in HCV-infected hepatoma cells : involvement of miR-491 in regulation of HCV via the PI3 kinase/Akt pathway (2011)
  • Author(s): Ishida H, Tatsumi T, Hosui A, Nawa T, Kodama T, Shimizu S, Hikita H, Hiramatsu N, Kanto T, Hayashi N, Takehara T
  • Journal Title: Biochem Biophys Res Commun Volume: Vol.412 Pages: 92-97
  • Peer Reviewed
• [Journal Article] Alterations in microRNA expression profile in HCV-infected hepatoma cells : involvement of miR-491 in regulation of HCV via the PI3 kinase/Akt pathway (2011)
  • Author(s): Ishida H, Tatsumi T, Takehara T, et al
  • Journal Title: Biochem Biophys Res Commun Volume: 412 Issue: 1 Pages: 92-97
  • DOI: 10.1016/j.bbrc.2011.07.049
  • Peer Reviewed
• [Journal Article] HCV感染により変動するマイクロRNAのHCV増殖に対する影響 (2010)
  • Author(s): 石田永、竹原徹郎、林紀夫
  • Journal Title: 消化器内科 Volume: 51巻 Pages: 636-641
• [Journal Article] HCV感染により変動するマイクロRRNAのHCV増殖に対する影響 (2010)
  • Author(s): 石田永、竹原徹郎、林紀夫
  • Journal Title: 消化器内科 Volume: 51 Pages: 636-641
• [Presentation] 分岐鎖アミノ酸のHCV増殖に与える影響 (2010)
  • Author(s): 石田永、竹原徹郎、林紀夫
  • Organizer: 第14回日本肝臓学会大会
  • Year and Date: 2010-10-13
• [Presentation] Perturbation of HCV replication by microRNAs which are regulated by HCV infection (2010)
  • Author(s): 石田永、竹原徹郎、林紀夫
  • Organizer: 17^<th> International Meeting on Hepatitis C Virus and Related Viruses
  • Year and Date: 2010-09-11
• [Presentation] Perturbation of HCV replication by microRNAs which are regulated by HCV infection (2009)
  • Author(s): 石田永、竹原徹郎、林紀夫
  • Organizer: The Liver Meeting 2009-AASLD's 60th Annual Meeting
  • Year and Date: 2009-11-01
• [Presentation] Perturbation of HCV replication by microRNAs which are regulated by HCV infection (2009)
  • Author(s): 石田永, 竹原徹郎, 林紀夫
  • Organizer: The Liver Meeting 2009-AASLD's 60th Annual Meeting
  • Place of Presentation: John B. Hynes Convention Center (Boston, USA)
  • Year and Date: 2009-11-01