Tyrosine phosphorylation of a viral protein in the hepatitis C virus life cycle

• Project/Area Number: 15K19021
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: University of Fukui
• Principal Investigator: Yamauchi Shota 福井大学, 学術研究院医学系部門, 特命助教 (00728941)
• Research Collaborator: SADA Kiyonao 福井大学, 学術研究院医学系部門, 教授 (10273765) ; CHIHARA Kazuyasu 福井大学, 学術研究院医学系部門, 准教授 (00314948) ; TAKEUCHI Kenji 福井大学, 学術研究院医学系部門, 助教 (40236419) ; HOTTA Hak 神戸大学, 大学院医学研究科, 教授 (40116249)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: C型肝炎ウイルス / インターフェロン / ウイルス-宿主相互作用 / チロシンキナーゼ

Outline of Final Research Achievements

More than 1.5 million people are infected with hepatitis C virus (HCV) in Japan. Following entry into the host hepatocyte, the RNA genome of HCV is translated into viral proteins and replicated by the viral proeins. Viral RNA and proteins are assembled into virus particles, which are released from the host hepatocyte through the secretory pathway and infect other hepatocytes. In this study, we found that tyrosine phosphorylation of the HCV NS5A protein by c-Abl promotes virus particle assembly. We also reveal the difference between the signaling mechanisms of the antiviral cytokines inteferon (IFN)-alpha and IFN-lambda.

Research Products

• [Journal Article] STAT1 is essential for the inhibition of hepatitis C virus replication by interferon-lambda but not by interferon-alpha (2016)
  • Author(s): Yamauchi, S., Takeuchi, K., Chihara, K., Honjoh, C., Kato, Y., Yoshiki, H., Hotta, H., and Sada, K.
  • Journal Title: Sci. Rep. Volume: 6 Issue: 1 Pages: 38336-38336
  • DOI: 10.1038/srep38336
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Hepatitis C virus particle assembly involves phosphorylation of NS5A by the c-Abl tyrosine kinase (2015)
  • Author(s): Yamauchi, S., Takeuchi, K., Chihara, K., Sun, X., Honjoh, C., Yoshiki, H., Hotta, H., and Sada, K.
  • Journal Title: J. Biol. Chem. Volume: 290 Issue: 36 Pages: 21857-21864
  • DOI: 10.1074/jbc.m115.666859
  • NAID: 120005973616
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Role of c-Abl in hepatitis C virus particle assembly (2015)
  • Author(s): Yamauchi, S., Takeuchi, K., Chihara, K., Sun, X., Honjoh, C., Yoshiki, H., Hotta, H., and Sada, K.
  • Organizer: 第38回日本分子生物学会年会・第88回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-02
• [Presentation] Role of NS5A tyrosine phosphorylation in hepatitis C virus particle assembly (2015)
  • Author(s): Yamauchi, S., Takeuchi, K., Chihara, K., Sun, X., Honjoh, C., Yoshiki, H., Hotta, H., and Sada, K.
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2015-11-23
• [Presentation] チロシンキナーゼによるHCV複製の制御機構 (2015)
  • Author(s): 山内翔太
  • Organizer: 第33回日本生化学会北陸支部大会
  • Place of Presentation: 富山
  • Year and Date: 2015-05-23
  • Invited