Analysis of induction of chronic hepatitis by HCV infection

• Project/Area Number: 20790354
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Virology
• Research Institution: Osaka University
• Principal Investigator: ABE Takayuki Osaka University, 微生物病研究所, 助教 (90403203)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 病原性 / HCV / TLR / CD44 / IP-10

Research Abstract

Although infiltration of lymphocytes and natural killer cells was observed in the liver of acute and chronic hepatitis C patients, the mechanisms of the liver injury during hepatitis C virus (HCV) infection are not well understood. Interferon-gamma-inducible protein 10 (IP-10), that selectively recruits activated T cells to the sites of inflammation, has shown to be expressed in the livers of the chronic hepatitis C patients. We have shown previously that IP-10 production was significantly enhanced in HCV RNA replicon cells and the human hepatoma cell lines infected with HCV through a TLR2-dependent signaling pathway. By the DNA microarray analysis, we have identified CD44 as a one of the candidates involved in the inflammatory response through a TLR signaling pathway. CD44 is a broadly distributed type I transmembrane glycoprotein and a receptor for glycosaminoglycan hyaluronan (HA). HA also works as a ligand for TLR2 and serum HA levels in the chronic hepatitis C patients were shown to increase according to the progression of liver fibrosis. IP-10 production was also induced by the treatment with HA in the replicon cells, but not in the naive cells. These results suggest that the IP-10 production in the HCV replicon cells is regulated by HA stimulation through the engagement of TLR2 and CD44, and that serum HA in chronic hepatitis C patients participates in the induction of IP-10.

Research Products

• [Journal Article] Host innate immune responses induced by baculovirus in mammals (2010)
  • Author(s): Abe T, Matsuura Y
  • Journal Title: Curr. Gene. Ther. (in press)
  • Peer Reviewed
• [Journal Article] Involvement of ceramide in the propagation of Japanese encephalitis virus (2010)
  • Author(s): Tani H, Shiokawa M, Kaname Y, Kanbara H, Mori Y, Abe T, Moriishi K, Matsuura Y
  • Journal Title: J. Virol. 84 Pages: 2798-2807
  • Peer Reviewed
• [Journal Article] Acquisition of complement resistance through incorporation of CD55/decay-accelerating factor into viral particles bearing baculovirus GP64 (2010)
  • Author(s): Kaname Y, Tani H, Kataoka C, Shiokawa M, Taguwa S, Abe T, Moriishi K, Kinoshita T, Matsuura Y
  • Journal Title: J. Virol. 84 Pages: 3210-3219
  • Peer Reviewed
• [Journal Article] Baculovirus induces type I interferon production through Toll-like receptor-dependent and -independent pathway in a cell-type specific manner (2009)
  • Author(s): Abe T, Kaname Y, Wen X, Tani H, Moriishi K, Uematsu S, Takeuchi O, Ishii KJ, Kawai T, Matsuura Y
  • Journal Title: J. Virol. 83 Pages: 7629-7640
  • Peer Reviewed
• [Journal Article] Cochaperone activity of human butyrate-induced transcript 1 facilitates hepatitis C virus replication through an Hsp90-dependent pathway (2009)
  • Author(s): Taguwa S, Kambara H, Omori H, Tani H, Abe T, Mori Y, Suzuki T, Yoshimori T, Moriishi K, Matsuura Y
  • Journal Title: J. Virol. 83 Pages: 10427-10436
  • Peer Reviewed
• [Journal Article] Human VAP-C negatively regulates hepatitis C virus propagation (2009)
  • Author(s): Kukihara H, Moriishi K, Taguwa S, Tani H, Abe T, Mori Y, Suzuki T, Fukuhara T, Taketomi A, Maehara Y, Matsuura Y
  • Journal Title: J. Virol. 83 Pages: 7959-7969
  • Peer Reviewed
• [Journal Article] Baculovirus induces type I interferon production through Toll-like receptor-dependent and -independent pathway in a cell-type-specific manner (2009)
  • Author(s): Abe T, Kaname Y, Wen X, Tani H, Moriishi K, Uematsu S, Takeuchi O, Ishii K J, Kawai T, Akira S, Matsuura Y
  • Journal Title: Journal of Virology Vol 83, No 15 Pages: 7629-7640
  • Peer Reviewed
• [Journal Article] Cochaperone activity of human butyrate-induced transcript 1 facilitates hepatitis C virus replication through an Hsp90-dependent pathway (2009)
  • Author(s): Taguwa S, Kambara H, Omori H, Tani H, Abe T, Mori Y, Suzuki T, Yoshimori T, Moriishi K, Matsuura Y
  • Journal Title: Journal of Virology Vol 83, No 20 Pages: 10427-10436
  • Peer Reviewed
• [Journal Article] Human VAP-C negatively regulates hepatitis C virus propagation (2009)
  • Author(s): Kukihara H, Moriishi K, Taguwa S, Tani H, Abe T, Mori Y, Suzuki T, Fukuhara T, Taketomi A, Maehara Y, Matsuura Y
  • Journal Title: Journal of Virology Vol 83, No 16 Pages: 7959-7969
  • Peer Reviewed
• [Journal Article] A single-amino-acid mutation in hepatitis C virus NS5A disruptingFKBP8 interaction impairs viral replication (2008)
  • Author(s): Okamoto T, Omori H, Kaname Y, Abe T, Nishimura y, Suzuki T, Miyamura T, Yoshimori T, Moriishi K, Matsuura Y
  • Journal Title: Journal of Virology Vol82, No7 Pages: 3480-3489
  • Peer Reviewed
• [Journal Article] Human butyrate-induced transcript-1 interacts with hepatitis C virus NS5A andregulates viral replication (2008)
  • Author(s): Taguwa S, Okamoto T, Abe T, Mori Y, Suzuki T, Moriishi K, Matsuura Y
  • Journal Title: Journal of Virology Vol82, No6 Pages: 2631-2641
  • Peer Reviewed
• [Presentation] ヒアルロン酸による炎症性ケモカインIP-10の過剰産生とC型肝炎の慢性化 (2009)
  • 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57回日本ウイルス学会学術集会
  • Place of Presentation: 都市センターホテル(東京都)
  • Year and Date: 2009-10-26
• [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 (2009)
  • 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57回日本ウイルス学会総会
  • Place of Presentation: 東京
• [Presentation] Hyaluronan participates in the IP-10 production in cells infected with HCV through an engagement of TLR2 and CD44 (2009)
  • Author(s): Abe T, Kaname Y, Moriishi K, Kanto T, Hayashi N, Matsuura Y
  • Organizer: 16th International symposium on HCV & related viruses
  • Place of Presentation: Nice
• [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、森石恒司、考藤達哉、林紀夫、松浦善治
  • Organizer: 第56回日本ウイルス学会学術集会
  • Place of Presentation: 岡山コンベンションセンター
  • Year and Date: 2008-10-26
• [Presentation] C型肝炎ウイルス感染による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 (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
  • Place of Presentation: 岡山
• [Presentation] Enhancement of IP-10 expression via TLR signaling pathway in cells expressing HCV proteins (2008)
  • Author(s): Abe T, Kaname Y, Wen X, Okamoto T, Moriishi K, Kanto T, Hayashi N, Matsuura Y
  • Organizer: 5th International symposium on HCV & related viruses
  • Place of Presentation: San Antonio
• [Book] C型肝炎ウイルスの持続感染機構 (2010)
  • Author(s): 阿部隆之、松浦善治
  • Publisher: 医学の門社
• [Book] Drug Delivery System(ワクチンベクターとしてのバキュロウイルス) (2009)
  • Author(s): 阿部隆之、谷英樹、松浦善治
  • Publisher: 日本医学館
• [Book] 肝・胆・膵、特集/C型肝炎のすべてHCVの宿主免疫回避機構とワクチン開発の現状 (2009)
  • Author(s): 阿部隆之、松浦善治
  • Publisher: 医歯薬出版株式会社
• [Book] Drug Delivery System/ワクチンベクターとしてのバキュロウイルス (2009)
  • Author(s): 阿部隆之、谷英樹、松浦善治
  • Publisher: 日本医学館
• [Book] 肝胆膵 特集・C型肝炎のすべて2009 Vol.57 No.5 Nov.2008 (2008)
  • Author(s): 阿部隆之、松浦善治
  • Total Pages: 1092
  • Publisher: (株)アークメディア