Entry mechanisms of visualized pseudotype virus bearing the envelope proteins of hepatitis C virus.

• Project/Area Number: 21790443
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Virology
• Research Institution: Osaka University
• Principal Investigator: TANI Hideki Osaka University, 微生物病研究所, 特任助教 (20397706)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 分子 / C型肝炎ウイルス(HCV) / シュードタイプウイルス / 組換えウイルス / 水疱性口内炎ウイルス / レセプター / テトラシステインタグ

Research Abstract

The receptors of HCV have been characterized, yet the entry pathways of the HCV into target cells are incompletely defined. As a surrogate virus system, pseudotype viruses transiently bearing HCV envelope proteins based on the vesicular stomatitis virus (VSV) and retrovirus or cell cultured HCV (HCVcc) have been developed. Here, we have tried to develop a fluorescence-labeled pseudotype VSV or recombinant VSV for a visualized investigation of the entry mechanisms. Furthermore, to characterize the mechanisms by which HCV infection activates downstream signaling pathways, we utilized a pseudotype vesicular stomatitis virus possessing HCV envelope proteins (HCVpv) and JFH-1 virus in combination with pharmacological inhibitors. We reported that HCV utilizes the phospholipase C (PLC) / protein kinase C (PKC)-dependent signaling for the entry. Inhibition of actin rearrangement by actin-depolymerizing reagents markedly diminishes HCVpv infection. Overall, these results indicate that the activation of PLC and PKC-dependent pathway is required for the entry of HCV and is involved in setting the actin rearrangement for the endocytosis of the virus.

Research Products

• [Journal Article] Elimination of hepatitis C virus from hepatocytes by a selective activation of therapeutic molecules. (2011)
  • Author(s): Xiaoyu Wen, Takayuki Abe, Hiroshi Kukihara, Shuhei Taguwa, Yoshio Mori, Hideki Tani, Nobuyuki Kato, Suzuki Tetsuro, Masashi Tatsumi, Kohji Moriishi, Yoshiharu Matsuura.
  • Journal Title: PLoS ONE. 6(1)
  • Peer Reviewed
• [Journal Article] Elimination of hepatitis C virus from hepatocytes by a selective activation of therapeutic molecules. (2011)
  • Author(s): Xiaoyu Wen, Takayuki Abe, Hiroshi Kukihara, Shuhei Taguwa, Yoshio Mori, Hideki Tani, Nobuyuki Kato, Suzuki Tetsuro, Masashi Tatsumi, Kohji Moriishi, Yoshiharu Matsuura.
  • Journal Title: PLoS ONE Volume: 6
  • Peer Reviewed
• [Journal Article] Acquisition of complement resistance through incorporation of CD55/DAF into viral particles bearing baculovirus GP64. (2010)
  • Author(s): Yuuki Kaname, Hideki Tani, Chikako Kataoka, Mai Shiokawa, Shuhei Taguwa, Takayuki Abe, Kohji Moriishi, Taroh Kinoshita, Yoshiharu Matsuura.
  • Journal Title: Journal of Virology. 84 Pages: 3210-3219
  • Peer Reviewed
• [Journal Article] Establishment of an indicator cell system for hepatitis C virus. (2010)
  • Author(s): Yoshinori Tanaka, Yoshio Mori, Hideki Tani, Takayuki Abe, Kohji Moriishi, Hirotatsu Kojima, Tetsuo Nagano, Takayoshi Okabe, Tetsuro Suzuki, Masashi Tatsumi, Yoshiharu Matsuura.
  • Journal Title: Microbiology and Immunology. 54 Pages: 206-220
  • NAID: 10029544486
  • Peer Reviewed
• [Journal Article] Procyanidin B1 purified from Cinnamomi cortex suppresses hepatitis C virus replication. (2010)
  • Author(s): Shenwei Li, Eiichi N Kodama, Yuuki Inoue, Hideki Tani, Yoshiharu Matsuura, Jing Zhang, Takashi Tanaka, Toshio Hattori.
  • Journal Title: Antiviral Chemistry & Chemotherapy. 20 Pages: 239-248
  • Peer Reviewed
• [Journal Article] Acquisition of complement resistance through incorporation of CD55/DAF into viral particles bearing baculovirus GP64. (2010)
  • Author(s): Yuuki Kaname, Hideki Tani, Chikako Kataoka, Mai Shiokawa, Shuhei Taguwa, Takayuki Abe, Kohji Moriishi, Taroh Kinoshita, Yoshiharu Matsuura.
  • Journal Title: Journal of Virology Volume: 84 Pages: 3210-3219
  • Peer Reviewed
• [Journal Article] Establishment of an indicator cell system for hepatitis C virus. (2010)
  • Author(s): Yoshinori Tanaka, Yoshio Mori, Hideki Tani, Takayuki Abe, Kohji Moriishi, Hirotatsu Kojima, Tetsuo Nagano, Takayoshi Okabe, Tetsuro Suzuki, Masashi Tatsumi, Yoshiharu Matsuura.
  • Journal Title: Microbiology and Immunology Volume: 54 Pages: 206-220
  • NAID: 10029544486
  • Peer Reviewed
• [Journal Article] Procyanidin B1 purified from Cinnamomi cortex suppresses hepatitis C virus replication. (2010)
  • Author(s): Shenwei Li, Eiichi N Kodama, Yuuki Inoue, Hideki Tani, Yoshiharu Matsuura, Jing Zhang, Takashi Tanaka, Toshio Hattori.
  • Journal Title: Antiviral Chemistry & Chemotherapy Volume: 20 Pages: 239-248
  • Peer Reviewed
• [Journal Article] Involvement of ceramide in the propagation of Japanese encephalitis virus. (2010)
  • Author(s): Hideki Tani, Mai Shiokawa, Yuuki Kaname, Hiroto Kambara, Yoshio Mori, Takayuki Abe, Kohji Moriishi, Yoshiharu Matsuura.
  • Journal Title: Journal of Virology 84 Pages: 2798-2807
  • Peer Reviewed
• [Journal Article] Human VAP-C negatively regulates hepatitis C virus propagation. (2009)
  • Author(s): Hiroshi Kukihara, Kohji Moriishi, Shuhei Taguwa, Hideki Tani, Takayuki Abe, Yoshio Mori, Tetsuro Suzuki, Takasuke Fukuhara, Akinobu Taketomi, Yoshihiko Maehara, Yoshiharu Matsuura.
  • Journal Title: Journal of Virology 83 Pages: 7959-7969
  • Peer Reviewed
• [Journal Article] Cochaperone activity of human butyrate-induced transcript 1 facilitates he patitis C virus replication through an Hsp90-dependent pathway. (2009)
  • Author(s): Shuhei Taguwa, Hiroto Kambara, Hiroko Omori, Hideki Tani, Takayuki Abe, Yoshio Mori, Tetsuro Suzuki, Tamotsu Yoshimori, Kohji Moriishi, Yoshiharu Matsuura.
  • Journal Title: Journal of Virology 83 Pages: 10427-10436
  • Peer Reviewed
• [Presentation] C型肝炎ウイルスの細胞侵入におけるフォスフォリパーゼCおよびプロテインキナーゼC依存的なシグナル伝達経路の関与 (2010)
  • Author(s): 谷英樹、阿部隆之、森石恆司、松浦善治
  • Organizer: 第58回日本ウイルス学会学術集会
  • Place of Presentation: 徳島
• [Presentation] Involvement of phospholipase C and protein kinase C-dependent signaling pathways in the entry of HCV. (2010)
  • Author(s): Hideki Tani, Takayuki Abe, Kohji Moriishi, Yoshiharu Matsuura
  • Organizer: 17th International Meeting on Hepatitis C Virus and Related Viruses.
  • Place of Presentation: Japan
• [Presentation] Intracellular delivery of serum-derived HCV. (2010)
  • Author(s): Takasuke Fukuhara, Hideki Tani, Mai Shiokawa, Takayuki Abe, Kohji Moriishi, Akinobu Taketomi, Yoshihiko Maehara, Yoshiharu Matsuura
  • Organizer: 17th International Meeting on Hepatitis C Virus and Related Viruses.
  • Place of Presentation: Japan
• [Presentation] Involvement of ceramide in the propagation of Japanese encephalitis virus. (2010)
  • Author(s): Hideki Tani, Mai Shiokawa, Yuuki Kaname, Hiroto Kambara, Yoshio Mori, Takayuki Abe, Kohji Moriishi, Yoshiharu Matsuura
  • Organizer: 9th International Symposium on positive-strand RNA viruses.
  • Place of Presentation: USA
• [Presentation] C型肝炎ウイルスの細胞侵入におけるフォスフォリパーゼCおよびプロテインキナーゼC依存的なシグナル伝達経路の関与 (2010)
  • Author(s): 谷英樹、阿部隆之、森石恆司、松浦善治
  • Organizer: 第58回日本ウイルス学会学術集会
  • Place of Presentation: 徳島・あわぎんホール
• [Presentation] Involvement of phospholipase C and protein kinase C-dependent signaling pathways in the entry of HCV. (2010)
  • Author(s): Hideki Tani, Takayuki Abe, Kohji Moriishi, Yoshiharu Matsuura.
  • Organizer: 17th International Meeting on Hepatitis C Virus and Related Viruses.
  • Place of Presentation: Japan・Yokohama
• [Presentation] Intracellular delivery of serum-derived HCV. (2010)
  • Author(s): Takasuke Fukuhara, Hideki Tani, Mai Shiokawa, Takayuki Abe, Kohji Moriishi, Akinobu Taketomi, Yoshihiko Maehara, Yoshiharu Matsuura.
  • Organizer: 17th International Meeting on Hepatitis C Virus and Related Viruses.
  • Place of Presentation: Japan・Yokohama
• [Presentation] Involvement of ceramide in the propagation of Japanese encephalitis virus. (2010)
  • Author(s): Hideki Tani, Mai Shiokawa, Yuuki Kaname, Hiroto Kambara, Yoshio Mori, Takayuki Abe, Kohji Moriishi, Yoshiharu Matsuura.
  • Organizer: 9th International Symposium on positive-strand RNA viruses.
  • Place of Presentation: Atlanta・USA
• [Presentation] 日本脳炎ウイルスの感染における脂質セラミドの役割 (2009)
  • Author(s): 谷英樹、塩川舞、寒原裕登、要祐喜、森嘉生、森石恆司、松浦善治
  • Organizer: 第57回日本ウイルス学会学術集会
  • Place of Presentation: 東京・都市センターホテル
  • Year and Date: 2009-10-26