Study on the regulatory mechanisms of infectious particle formation of hepatitis C virus by arachidonic acid cascade

• Project/Area Number: 15K08495
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: Kyoto University
• Principal Investigator: Hjijikata Makoto 京都大学, ウイルス・再生医科学研究所, 准教授 (90202275)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: C型肝炎ウイルス / 感染性粒子産生 / アラキドン酸カスケード / トロンボキサン合成酵素 / 阻害剤 / 感染性 / 培養細胞 / HCV / 粒子形成 / トロンボキサン / TXAS / 遺伝子発現 / 感染性粒子

Outline of Final Research Achievements

Molecular Mechanisms for the inhibition of infectious hepatitis C virus particle formation by thromboxane A2 synthase inhibitor, Oxagrel, was examined in detail by several techniques. Microarray and CAGE analyses have showed no informative result. Metabolite study, however, showed that the reduction of hexanoic acid (HA), a fatty acid with pentatonic carbon chain, was caused in the cells treated with Oxagrel. The contribution of HA to the infectious HCV particle formation was not cleared yet. It seemed to be a novel finding that the amount of HA in the cells was changed by TXAS inhibitor.

Research Products

• [Journal Article] Broad-spectrum antiviral agents: secreted phospholipase A2 targets viral envelope lipid bilayers derived from the endoplasmic reticulum membrane (2017)
  • Author(s): Ming Chen, Chie Aoki-Utsubo, Masanori Kameoka, Lin Deng, Yutaka Terada, Wataru Kamitani, Kei Sato, Yoshio Koyanagi, Makoto Hijikata, Keiko Shindo, Takeshi Noda, Michinori Kohara & Hak Hotta.
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 15931-15931
  • DOI: 10.1038/s41598-017-16130-w
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Liver-specific mono-unsaturated fatty acid synthase-1 inhibitor for anti-hepatitis C treatment (2016)
  • Author(s): Nio Y., Hasegawa H., Okamura H., Miyayama Y., Akahori Y., Hijikata M.
  • Journal Title: Antiviral Research Volume: 132 Pages: 262-267
  • DOI: 10.1016/j.antiviral.2016.07.003
  • Peer Reviewed
• [Presentation] Development of novel recombinant HCV1b culture system. (2017)
  • Author(s): Miyayama Y., Chayama H., Miki D., Imamura M., Chayama K., Hijikata M.
  • Organizer: 第65回日本ウイルス学会学術集会
• [Presentation] Liver-specific mono-unsaturated fatty acid synthase-1 inhibitor as one option for anti-hepatitis C treatment (2016)
  • Author(s): Hasegawa H., Nio Y., Okamura H., Miyayama Y., Akahori Y., Hijikata M.
  • Organizer: 23th International Symposium on Hepatitis C Virus and Related Viruses
  • Place of Presentation: Kyopto Japan
  • Year and Date: 2016-10-11
  • Int'l Joint Research