Study on the lipid biosynthesis and the related phathology in. hepatitis C virus infection

• Project/Area Number: 19590473
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: Osaka University
• Principal Investigator: MORIISHI Koji Osaka University, 微生物病研究所, 准教授 (90260273)
• Co-Investigator(Kenkyū-buntansha): MORIISHI Koji 大阪大学, 微生物病研究所, 准教授 (90260273)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 病原性 / ウイルス / 感染症 / 発現制御 / C型肝炎 / C型肝炎ウイルス / HCV / 肝脂肪化 / SPP / 膜内プロテアーゼ / 脂質

Research Abstract

C型肝炎ウイルス(HCV)コア蛋白質は、細胞内のラフト様構造にも局在してるが、ウイルス感染環あるいは病原性における役割はわかっていない。本研究によって、膜内切断を受けたコア蛋白質はウイルス粒子形成に必要であることが示された。また、コア蛋白質とPA28γの発現によって脂質代謝が増強される現象は、インターフェロン抵抗性を示すC型肝炎患者で多く認められるコア蛋白質変異によって減弱していた。以上のことから、コア蛋白質を修飾する宿主蛋白質を標的にした薬剤が、抗HCV薬として期待出来ることが分かった

Research Products

• [Journal Article] 2008. Hepatitis C virus core protein : its coordinate roles with PA28gamma in metabolic abnormality and carcinogenicity in the liver (2008)
  • Author(s): Mori, Y., K. Moriishi, and Y. Matsuura
  • Journal Title: Int. J. Biochem. Cell Biol 40 Pages: 1437-1442
• [Journal Article] Intramembrane processing by signal peptide peptidase regulates the membrane localization of hepatitis C virus core protein and viral propagation (2008)
  • Author(s): Okamoto, K., Y. Mori, Y. Komoda, T. Okamoto, M. Okochi, M. Takeda, T. Suzuki, K. Moriishi, and Y. Matsuura
  • Journal Title: J. Virol 82 Pages: 8349-8361
• [Journal Article] A single-amino-acid mutation in hepatitis C virus NS5A disrupting FKBP8 interaction impairs viral replication (2008)
  • Author(s): Okamoto, T., H. Omori, Y. Kaname, T. Abe, Y. Nishimura, T. Suzuki, T. Miyamura, T. Yoshimori, K. Moriishi, and Y. Matsuura
  • Journal Title: J. Virol 82 Pages: 3480-3489
• [Journal Article] Human butyrate-induced transcript 1 interacts with hepatitis C virus NS5A and regulates viral replication (2008)
  • Author(s): Taguwa, S., T. Okamoto, T. Abe, Y. Mori, T. Suzuki, K. Moriishi, and Y. Matsuura
  • Journal Title: J. Virol 82 Pages: 2631-2641
• [Journal Article] Hepatitis C virus core protein : its coordinate roles with PA28gamma in metabolic abnormality and carcinogenicity in the liver. (2008)
  • Author(s): Mori, Y.
  • Journal Title: Int. J. Biochem. Cell Biol. 40 Pages: 1437-1442
  • Peer Reviewed
• [Journal Article] Intramembrane processing by signal peptide peptidase regulates the membrane localization of hepatitis C virus core protein and viral propagation. (2008)
  • Author(s): Okamoto, K
  • Journal Title: J. Virol. 82 Pages: 2631-2641
  • Peer Reviewed
• [Journal Article] A single-amino-acid mutation in hepatitis C virus NS5A disrupting FKBP8 interaction impairs viral replication (2008)
  • Author(s): Okamoto, T.
  • Journal Title: J. Virol. 82 Pages: 2631-2641
  • Peer Reviewed
• [Journal Article] Human butyrate-induced transcript 1 interacts with hepatitis C virus NS5A and regulates viral replication. (2008)
  • Author(s): Taguwa, S
  • Journal Title: J. Virol. 82 Pages: 2631-2641
  • Peer Reviewed
• [Journal Article] Human butyrate-induced transcript 1 interacts with hepatitis C virus NS5A and regulates viral replication. (2008)
  • Author(s): Taguwa S.
  • Journal Title: J. Virol. 82 Pages: 2631-2641
  • Peer Reviewed
• [Journal Article] Critical role of PA28γ in hepatitis C virus-associated steatogenesis and hepatocarcinogenesis (2007)
  • Author(s): Moriishi K., Mochizuki R., Moriya K., Miyamoto H., Mori Y., Abe T., Murata S., Tanaka K., Miyamura T., Suzuki T., Koike K., and Matsuura Y
  • Journal Title: Proc. Natl Acad. Sci. USA 104 Pages: 1661-1666
• [Journal Article] Hepatitis C Virus Nonstructural Protein 5A Modulates TLR-MyD88-Dependent Signaling Pathway in the Macrophage Cell Lines (2007)
  • Author(s): Abe T., Kaname Y., Hamamoto I., Tsuda Y., Wen X., Taguwa S., Moriishi K., Takeuchi O., Kawai T., Kanto T., Hayashi N., Akira S., and Matsuura Y
  • Journal Title: J. Virol 81 Pages: 8953-8966
• [Journal Article] Processing of Capsid Protein by Cathepsin L Plays a Crucial Role in Replication of the Japanese Encephalitis Virus in Neural and Macrophage Cells (2007)
  • Author(s): Mori Y., Yamashita T., Tanaka Y., Tsuda Y., Abe T., Moriishi K., and Matsuura Y
  • Journal Title: J. Virol 81 Pages: 8477-8487
• [Journal Article] Replication-competent recombinant vesicular stomatitis virus encoding hepatitis C virus envelope proteins (2007)
  • Author(s): Tani H., Komoda Y., Matsuo E., Suzuki K., Hamamoto I., Yamashita T., Moriishi K., Fujiyama K., Kanto T., Hayashi N., Owsianka A., Patel A.H., Whitt M.A., and Matsuura Y
  • Journal Title: J. Virol 81 Pages: 8601-8612
• [Journal Article] Host factors involved in the replication of hepatitis C virus (2007)
  • Author(s): Moriishi K., and Matsuura Y
  • Journal Title: Rev. Med. Virol. 17 Pages: 343-354
• [Journal Article] Evaluation systems for anti HCV drugs (2007)
  • Author(s): Moriishi K., and Matsuura Y
  • Journal Title: Adv. Drug Deliv. Rev 59 Pages: 1213-1221
• [Journal Article] Involvement of the PA28gamma-dependent pathway in insulin resistance induced by hepatitis C virus core protein (2007)
  • Author(s): Miyamoto H., Moriishi K, Moriya K, Murata S, Tanaka K, Suzuki T, Miyamura T, Koike K, Matsuura Y
  • Journal Title: J. Virol 81 Pages: 1727-1735
• [Journal Article] Hepatitis C Virus Nonstructural Protein 5A Modulates TLR-My D88-Dependent Signaling Pathway in the Macrophage Cell Lines. (2007)
  • Author(s): Abe T.
  • Journal Title: J. Virol. 81 Pages: 8953-8966
  • Peer Reviewed
• [Journal Article] Processing of Capsid Protein by Cathepsin L Plays a Crucial Role in Replication of the Japanese Encephalitis Virus in Neural and Macrophage Cells. (2007)
  • Author(s): Mori Y.
  • Journal Title: J. Virol. 81 Pages: 8477-8487
  • Peer Reviewed
• [Journal Article] Host factors involved in the replication of hepatitis C virus. (2007)
  • Author(s): Moriishi K.
  • Journal Title: Rev. Med. Virol. 17 Pages: 343-354
  • Peer Reviewed
• [Journal Article] Evaluation systems for anti-HCV drug (2007)
  • Author(s): Moriishi K.
  • Journal Title: Adv. Drug. Deliv. Rev. 59 Pages: 1213-1221
  • Peer Reviewed
• [Presentation] C 型肝炎ウイルス感染と肝発癌 (2008)
  • Author(s): 森石恆司、松浦善治
  • Organizer: 第82回日本感染症学会総会、教育講演
  • Place of Presentation: 松江
• [Presentation] C 型肝炎ウイルス感染によるTLR 経路を介した炎症性ケモカインIP- 10 の過剰産生 (2008)
  • Author(s): 阿部隆之、要祐喜、森石恆司、考藤達哉、林紀夫、松浦善治
  • Organizer: 第56回日本ウイルス学会総会(ワークショップ)
  • Place of Presentation: 岡山
• [Presentation] 日本脳炎ウイルスの細胞侵入におけるセラミドの関与 (2008)
  • Author(s): 谷英樹、泉貴之、寒原裕登、要祐喜、森嘉生、森石恆司、松浦善治
  • Organizer: 第56回日本ウイルス学会総会(一般口演)
  • Place of Presentation: 岡山
• [Presentation] C 型肝炎ウイルスの複製におけるhB-ind1 のコシャペロン活性 (2008)
  • Author(s): 田鍬修平、阿部隆之、森嘉生、森石恆司、松浦善治
  • Organizer: 第56回日本ウイルス学会総会(一般口演)
  • Place of Presentation: 岡山
• [Presentation] C 型肝炎ウイルス感染におけるプロテアソーム活性化蛋白質PA28γの役割 (2008)
  • Author(s): 森石恆司、松浦善治
  • Organizer: 第56回日本ウイルス学会総会(一般口演)
  • Place of Presentation: 岡山
• [Presentation] ヒトVAP-CはC 型肝炎ウイルスの複製を抑制する (2008)
  • Author(s): 久木原博、森石恆司、松浦善治
  • Organizer: 第56回日本ウイルス学会総会(一般口演)
  • Place of Presentation: 岡山
• [Presentation] Ceramide plays a crucial role on theentry of Japanese encephalitis virus (2008)
  • Author(s): Tani, H, Izumi, T., Kanbara, H., Kaname, Y., Mori, Y., Moriishi, K., Matsuura, Y.
  • Organizer: 15th International Symposium on Hepatitis C virus & related viruses, San Antonio, USA
• [Presentation] HCV infection induces IP-10 production through the TLR signaling pathway (2008)
  • Author(s): Abe, T., Kaname, Y., Moriishi, K., Kanto, T., Hayashi, N., Matsuura, Y
  • Organizer: 15th International Symposium on Hepatitis Cvirus & related viruses, San Antonio, USA
• [Presentation] Human vesicule-associated membrane protein-associated protein subtype Cinhibits HCV replication (2008)
  • Author(s): Kukihara, H., Moriishi, K., Matsuura, Y.
  • Organizer: 15th International Symposium on Hepatitis Cvirus & related viruses, San Antonio, USA
• [Presentation] Establishment of an indicator cell line that detects the replication of HCV insera from hepatitis C patients (2008)
  • Author(s): Tanaka, Y., Mori, Y., Tani, H., Abe, T., Moriishi, K., Matsuura, Y.
  • Organizer: 15th International Symposium on Hepatitis Cvirus & related viruses, San Antonio, USA
• [Presentation] Proteasome activator PA28gamma is required for efficient growth of hepatitis C virus (2008)
  • Author(s): Moriishi, K., Matsuura, Y
  • Organizer: 15th International Symposium on Hepatitis C virus & related viruses, San Antonio, USA
• [Presentation] C型肝炎ウイルス感染と肝発癌 (2008)
  • Author(s): 森石恆司
  • Organizer: 第82回日本感染症学会総会
  • Place of Presentation: 島根県松江市
• [Presentation] C型肝炎ウイルス感染によるTLR経路を介した炎症性ケモカインIP-10の過剰産生 (2008)
  • Author(s): 阿部隆之
  • Organizer: 第56回日本ウイルス学会総会
  • Place of Presentation: 岡山県岡山市
• [Presentation] 日本脳炎ウイルスの細胞侵入におけるセラミドの関与、 (2008)
  • Author(s): 谷英樹
  • Organizer: 第56回日本ウイルス学会総会
  • Place of Presentation: 岡山県岡山市
• [Presentation] C型肝炎ウイルスの複製におけるhB-indlのコシャペロン活性、 (2008)
  • Author(s): 田鍬修平
  • Organizer: 第56回日本ウイルス学会総会
  • Place of Presentation: 岡山県岡山市
• [Presentation] C型肝炎ウイルス感染におけるプロテアソーム活性化蛋白質PA28γの役割 (2008)
  • Author(s): 森石恆司
  • Organizer: 第56回日本ウイルス学会総会
  • Place of Presentation: 岡山県岡山市
• [Presentation] ヒトVAP-CはC型肝炎ウイルスの複製を抑制する。 (2008)
  • Author(s): 久木原博
  • Organizer: 第56回日本ウイルス学会総会
  • Place of Presentation: 岡山県岡山市
• [Presentation] 患者血清中に存在するC型肝炎ウイルスの感染複製を検出可能な指示細胞の樹立 (2008)
  • Author(s): 田中佳典
  • Organizer: 第56回日本ウイルス学会総会
  • Place of Presentation: 岡山県岡山市
• [Presentation] Ceramide plays a crucial role on the entry of Japanese encephalitis virus (2008)
  • Author(s): Tani, H
  • Organizer: 15^<th> International Symposium on Hepatitis Cvirus & related viruses
  • Place of Presentation: San Antonio, USA
• [Presentation] Human vesicule-associated membrane protein-associated protein subtype C inhibits HCV replication. (2008)
  • Author(s): Kukihara, H
  • Organizer: 15^<th> International Symposium on Hepatitis C virus & related viruses
  • Place of Presentation: San Antonio, USA
• [Presentation] HCV infection induces IP-10 production through the TLR signaling pathway. (2008)
  • Author(s): Abe, T
  • Organizer: 15^<th> International Symposium on Hepatitis C virus & related viruses
  • Place of Presentation: San Antonio, USA
• [Presentation] Establishment of an indicator cell line that detects the replication of HCV insera from hepatitis C patients. (2008)
  • Author(s): Tanaka, Y.
  • Organizer: 15^<th> International Symposium on Hepatitis C virus & related viruses
  • Place of Presentation: San Antonio, USA
• [Presentation] PA28gamma is required for efficient growth of hepatitis C virus. (2008)
  • Author(s): Moriishi, K.
  • Organizer: 15^th International Symposium on Hepatitis C virus & related viruses
  • Place of Presentation: San Antonio, USA
• [Presentation] Critical role of REGγ/PA28γ-proteasome pathway in hepatitis C virus-associated steatogenesis and hepatocarcinogenesis (2007)
  • Author(s): Kohji Moriishi
  • Organizer: 2007 International RIMD-CVRDC Joint Symposium
  • Place of Presentation: Osaka
  • Year and Date: 2007-12-18
• [Presentation] Critical role of REG γ/PA28 γ-proteasome pathway in hepatitis C virus-associated steatogenesis and hepatocarcinogenesis (2007)
  • Author(s): Moriishi K.
  • Organizer: International RIMD-CVRDC Joint Symposium
  • Place of Presentation: 吹田市
  • Year and Date: 2007-12-18
• [Presentation] Matsuura : Human butyrate-induced transcript 1 interacts with HCV NS5A and regulates HCV replication (2007)
  • Author(s): Shuhei Taguwa, Toru Okamoto, Takayuki Abe, Kohji Moriishi, and Yoshiharu
  • Organizer: 14th International Meeting on HCV and Related Viruses, Glasgow
• [Presentation] Enhancement of IP-10 expression via TLR signaling pathway in cells expressing HCV proteins (2007)
  • Author(s): Takayuki Abe, Yuuki Kaname, Xiaoyu Wen, Kohji Moriishi, Tatsuya Kanto, Norio Hayashi, and Yoshiharu Matsuura
  • Organizer: 4th International Meeting on HCV and Related Viruses, Glasgow
• [Presentation] Replication-competent recombinantvesicular stomatitis virus encoding HCV envelope proteins. (2007)
  • Author(s): Hideki Tani, Yasumasa Komoda, Eiko Matsuo, Kensuke Suzuki, Itsuki Hamamoto, Tetsuo Yamashita, Kohji Moriishi, Kazuhito Fujiyama, Tatsuya Kanto, Norio Hayashi, Ania Owsianka, Arvind H. Patel, Michael A. Whitt, and Yoshiharu Matsuura
  • Organizer: 4th International Meeting on HCV and Related Viruses, Glasgow
• [Presentation] Intramembrane processing by SPP regulates membrane localization of HCV core protein and viral propagation. (2007)
  • Author(s): Yoshio Mori, Kiyoko Okamoto, Toru Okamoto, Yasumasa Komoda, Masayasu Okochi, Masatoshi Takeda, Tetsuro Suzuki, Kohji Moriishi, and Yoshiharu Matsuura
  • Organizer: 4th International Meeting on HCV and Related Viruses, Glasgow
• [Presentation] FKBP8 Plays a Crucial Role in the Replication of Hepatitis C Virus (2007)
  • Author(s): Toru Okamoto, Kohji Moriishi, and Yoshiharu Matsuura
  • Organizer: HEP DART 2007
  • Place of Presentation: Hawaii
• [Presentation] HCV コア蛋白質による脂肪酸合成促進と肝細胞癌発症におけるPA28γ の役割 (2007)
  • Author(s): 森石恆司、森屋恭爾、村田茂穂、田中啓二、鈴木哲朗、宮村達男、小池和彦、松浦善治
  • Organizer: 第43回日本肝臓学会総会ワークショップ
  • Place of Presentation: 東京
• [Presentation] C 型肝炎ウイルスゲノム複製に関与する宿主蛋白質B-ind1 の機能解析 (2007)
  • Author(s): 田鍬修平、岡本 徹、阿部隆之、森 嘉生、森石恆司、松浦善治
  • Organizer: 第55回日本ウイルス学会総会
  • Place of Presentation: 札幌
• [Presentation] C 型肝炎ウイルスによるTLR シグナル伝達経路を介した炎症性ケモカインIP-10 の過剰産生 (2007)
  • Author(s): 阿部隆之、森石恆司、考藤達哉、林紀夫、審良静男、松浦善治
  • Organizer: 第55回日本ウイルス学会総会
  • Place of Presentation: 札幌
• [Presentation] シュードタイプと組換え水疱性口内炎ウイルスを用いたC 型肝炎ウイルスの感染機構の解析 (2007)
  • Author(s): 谷英樹、菰田泰正、鈴木健介、山下哲生、稲田大彦、森石恆司、考藤達哉、林紀夫、松浦善治
  • Organizer: 第55回日本ウイルス学会総会
  • Place of Presentation: 札幌
• [Presentation] C 型肝炎ウイルスゲノム複製におけるFKBP8 の役割 (2007)
  • Author(s): 岡本徹、森石恆司、松浦善治
  • Organizer: 第55回日本ウイルス学会総会
  • Place of Presentation: 札幌
• [Presentation] C型肝炎ウイルスコア蛋白質のシグナルペプチドペプチダーゼによるプロセッシングの生物学的意義 (2007)
  • Author(s): 森嘉生、岡本貴世子、岡本徹、菰田泰正、鈴木哲朗、森石恆司、松浦善治
  • Organizer: 第55回日本ウイルス学会総会
  • Place of Presentation: 札幌
• [Presentation] Critical role of PA28 γ-proteasome pathway in hepatitis C virus-associated steatogenesis and hepatocarcinogenesis (2007)
  • Author(s): Kohji Moriishi
  • Organizer: 7th Awaji International forum on infection and immunology
  • Place of Presentation: Awaji
• [Presentation] Human butyrate-induced transcript 1 interacts with HCV NS5A and regulates HCV replication. (2007)
  • Author(s): Taguwa S.
  • Organizer: 14th International Meeting on HCV and Related Viruses
  • Place of Presentation: Glasgow, UK
• [Presentation] Intramembrane processing by SPP regulates membrane localization of HCV core protein and viral propagation. (2007)
  • Author(s): Mori Y.
  • Organizer: 14th International Meeting on HCV and Related Viruses
  • Place of Presentation: Glasgow, UK
• [Presentation] C型肝炎ウイルスゲノム複製に関与する宿主蛋白質B-indlの機能解析 (2007)
  • Author(s): 田鍬修平
  • Organizer: 第55回日本ウイルス学会総会
  • Place of Presentation: 札幌
• [Presentation] Critical role of PA28 γ-proteasome pathway in hepatitis C virus-associated steatogenesis and hepatocarcinogenesis. (2007)
  • Author(s): Moriishi K.
  • Organizer: 7th Awaji International forum on infection and immunology
  • Place of Presentation: 淡路市
• [Remarks]
  • URL: http://www.dma.jim.osaka-u.ac.jp/kg-portal/aspi/RX0011D.asp?UNO=123O3&page=