Molecular mechanism of hepatitis C virus-induced lipid droplet formation

• Project/Area Number: 26461003
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kobe University
• Principal Investigator: SHOJI Ikuo 神戸大学, 医学研究科, 教授 (40356241)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: HCV / 脂肪滴 / NS3/4A プロテアーゼ / 脂肪化 / 肝炎 / 肝癌 / 肝脂肪化 / ウイルス増殖

Outline of Final Research Achievements

(1) SPG20 was cleaved in HCVcc-infected Huh-7.5 cells. (2) Transient expression of HCV NS3/4A resulted in cleavage of SPG20. (3) Inactive mutant NS3/4A did not cleave SPG20. (4) NS3/4A inhibitor inhibited cleavage of SPG20, whereas NS5A inhibitor did not inhibit cleavage of SPG20. (5) Treatment of the HCVcc-infected Huh-7.5 cells decreased the size of lipid droplets. Taken together, our results suggest that HCV NS3/4A cleaves SPG20 thereby promoting enlargement of lipid droplet in HCV-infected cells.

Research Products

• [Journal Article] Hepatitis C virus NS5A protein interacts with lysine methyltransferase SET and MYND domain-containing 3 and induces activator protein 1 activation. (2016)
  • Author(s): Chen M, Gan X, Yoshino K, Kitakawa M, Shoji I, Deng L, Hotta H.
  • Journal Title: Microbiol Immunol. Volume: 60 Issue: 6 Pages: 407-417
  • DOI: 10.1111/1348-0421.12383
  • Peer Reviewed / Open Access
• [Journal Article] TRC8-dependent degradation of hepatitis C virus immature core protein regulates viral propagation and pathogenesis. (2016)
  • Author(s): Aizawa S., Okamoto T., Sugiyama Y., Kouwaki T., Ito A., Suzuki T., Ono C., Fukuhara T., Yamamoto M., Okochi M., Hiraga N., Imamura M., Chayama K., Suzuki R., Shoji I., Moriishi K., Moriya K., Koike K., and Matsuura Y.
  • Journal Title: Nat. Commun. Volume: 7 Issue: 1 Pages: 1-12
  • DOI: 10.1038/ncomms11379
  • Peer Reviewed / Open Access
• [Journal Article] Physical and functional interaction between hepatitis C virus NS5A protein and ovarian tumor protein deubiquitinase 7B. (2015)
  • Author(s): Sianipar IR, Matsui C, Minami N, Gan X, Deng L, Hotta H, and Shoji I
  • Journal Title: Microbiology and Immunology Volume: 59 Issue: 8 Pages: 466-476
  • DOI: 10.1111/1348-0421.12278
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A single-amino-acid mutation in hepatitis C virus NS5A disrupts physical and functional interaction with the transcription factor HNF-1α. (2015)
  • Author(s): Matsui C, Sianipar IR, Minami N, Deng L, Hotta H, and Shoji I.
  • Journal Title: Journal of General Virology Volume: 96 Issue: 8 Pages: 2200-2205
  • DOI: 10.1099/vir.0.000179
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] HCV upregulates Bim through the ROS/JNK signalling pathway, leading to Bax-mediated apoptosis. (2015)
  • Author(s): Deng L, Chen M, Tanaka M, Ku Y, Itoh T, Shoji I, Hotta H
  • Journal Title: J Gen Virol Volume: 96 Issue: 9 Pages: 2670-2683
  • DOI: 10.1099/jgv.0.000221
  • Peer Reviewed
• [Journal Article] Induction of cell-mediated immune responses in mice by DNA vaccines that express hepatitis C virus NS3 mutants lacking serine protease and NTPase/RNA helicase activities. (2014)
  • Author(s): Ratnoglik SL, Jiang DP, Aoki C, Sudarmono P, Shoji I, Deng L, Hotta H
  • Journal Title: PLoS One Volume: 9(6) Issue: 6 Pages: 1-9
  • DOI: 10.1371/journal.pone.0098877
  • NAID: 120005705278
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Nitrosative stress induces peroxiredoxin 1 ubiquitination during ischemic insult via E6AP activation in endothelial cells both in vitro and in vivo (2014)
  • Author(s): Tao RR, Wang H, Hong LJ, Huang JY, Lu YM, Liao MH, Ye WF, Lu NN, Zhu DY, Huang Q, Fukunaga K, Lou YJ, Shoji I, Wilcox CS, Lai EY, Han F
  • Journal Title: Antioxid Redox Signal Volume: (in press) Issue: 1 Pages: 1-16
  • DOI: 10.1089/ars.2013.5381
  • Peer Reviewed / Open Access
• [Presentation] Molecular mechanism of HCV-induced lysosomal degradation of HNF-1α protein (2016)
  • Author(s): Matsui C, Minami N, Deng L, Shoji I
  • Organizer: 第64回日本ウイルス学会学術集会
  • Place of Presentation: 札幌、札幌コンベンションセンター
  • Year and Date: 2016-10-23
• [Presentation] Molecular mechanism of HCV-induced lysosomal degradation of HNF-1α protein. (2016)
  • Author(s): Matsui C, Minami N, Deng L, and Shoji I.
  • Organizer: The 23rd International Symposium on Hepatitis C Virus and Related Viruses
  • Place of Presentation: 京都、国立京都国際会館
  • Year and Date: 2016-10-11
  • Int'l Joint Research
• [Presentation] C型肝炎ウイルス基礎研究の最近の話題 (2016)
  • Author(s): 勝二郁夫
  • Organizer: 第11回神戸肝疾患治療研究会
  • Place of Presentation: 神戸
  • Year and Date: 2016-02-12
  • Invited
• [Presentation] A novel pathway for lipid droplet formation induced by hepatitis C virus (2015)
  • Author(s): Chieko Matsui, Imelda Rosalyn Sianipar, Nanae Minami, Ming Chen, Lin Deng, Hak Hotta, Ikuo Shoji
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 博多
  • Year and Date: 2015-11-22
• [Presentation] Physical and functional interaction between hepatitis C virus NS5A protein and ovarian tumor protein deubiquitinase 7B (2015)
  • Author(s): Imelda R Sianipar, Chieko Matsui, Nanae Minami, Ming Chen, Xiang Gan, Lin Deng, Hak Hotta, Ikuo Shoji
  • Organizer: 22th International Symposium on Hepatitis C Virus and Related Viruses
  • Place of Presentation: Strasbourg, France
  • Year and Date: 2015-10-09
  • Int'l Joint Research
• [Presentation] C型肝炎ウイルスとプロテアソーム経路 (2015)
  • Author(s): 勝二郁夫
  • Organizer: 第21回大阪府立母子保健総合医療センターシンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 2015-02-12
  • Invited
• [Presentation] C型肝炎ウイルス研究の新展開 (2014)
  • Author(s): 勝二郁夫
  • Organizer: 千里ライフサイエンスセミナー 免疫・感染症シリーズ第5回「話題のウイルス感染症の正体とその対策」
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-24
  • Invited