C型肝炎ウイルスの組織親和性の解析

• Project Area: Molecular basis of host cell competency in virus infection
• Project/Area Number: 25115511
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Osaka University
• Principal Investigator: 松浦 善治 大阪大学, 微生物病研究所, 教授 (50157252)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000); Fiscal Year 2014: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000); Fiscal Year 2013: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
• Keywords: HCV / miR-122 / 宿主因子 / 組織親和性

Outline of Annual Research Achievements

C型肝炎ウイルス(HCV)は肝臓で増殖するが、親和性の決定機構は不明な点が多い。肝臓特異的なマイクロRNAであるmiR-122は、非肝臓細胞ではほとんど検出されない。miR-122を強制発現させた非肝臓細胞株にHCVを接種すると、いくつかの細胞株でゲノム複製が観察されるが、感染性粒子は産生されない。非肝臓細胞株は肝臓細胞に比べて、超低比重リポ蛋白質の産生に関与するアポリポ蛋白質の発現が有意に低いことから、HCVの肝臓親和性は、マイクロRNAや脂質代謝系によって規定されていることが示唆された)。次に、α-fetoproteinの発現を指標にして肝機能を保持した細胞株を選択し、ヒト胃癌由来のFU97細胞がmiR-122を強制発現しなくても、肝臓由来のHuh7細胞と同等のHCV感受性を示すことを見いだした。FU97細胞は薬剤やウイルス株に関して、肝臓由来のHuh7細胞とは異なる性状を示すことから、HCVの増殖に関与する新しい宿主因子や新規治療薬の探索への応用が期待される。

Research Progress Status

26年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

26年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Novel permissive cell lines for complete propagation of hepatitis C virus. (2014)
  • Author(s): Shiokawa M, Fukuhara T, Ono C, Yamamoto S, Okamoto T, Watanabe N, Wakita T, Matsuura Y.
  • Journal Title: J Virol. Volume: 88(10) Issue: 10 Pages: 5578-94
  • DOI: 10.1128/jvi.03839-13
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Amphipathic α-Helices in Apolipoproteins Are Crucial to the Formation of Infectious Hepatitis C Virus Particles (2014)
  • Author(s): Fukuhara T, Wada M, Nakamura S, Ono C, Shiokawa M, Yamamoto S, Motomura T, Okamoto T, Okuzaki D, Yamamoto M, Saito I, Wakita T, Koike K, Matsuura Y
  • Journal Title: PLoS Pathog Volume: 10(12) Issue: 12 Pages: e1004534-e1004534
  • DOI: 10.1371/journal.ppat.1004534
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Innate immune response induced by baculovirus attenuates transgene expression in mammalian cells. (2014)
  • Author(s): Ono C., Ninomiya A., Yamamoto S., Abe T., Wen X., Fukuhara T., Sasai M., Yamamoto M., Saitoh T., Satoh T., Kawai T., Ishii J. K., Akira S., Okamoto T., and Matsuura Y.
  • Journal Title: Journal of Virology Volume: 88 Issue: 4 Pages: 2157-2167
  • DOI: 10.1128/jvi.03055-13
  • Peer Reviewed
• [Journal Article] Japanese encephalitis virus core protein inhibits stress granule formation through an interaction with Caprin-1 and facilitates viral propagation. (2013)
  • Author(s): Hiroshi Katoh
  • Journal Title: Journal of Virology Volume: 87(1) Issue: 1 Pages: 489-502
  • DOI: 10.1128/jvi.02186-12
  • Peer Reviewed
• [Journal Article] Ifit1 inhibits Japanese encephalitis virus replication through binding to 5' capped 2'-O unmethylated RNA. (2013)
  • Author(s): Kimura T, Katoh H, Kayama H, Saiga H, Okuyama M, Okamoto T, Umemoto E, Matsuura Y, Yamamoto M, Takeda K
  • Journal Title: J. Virology Volume: 87 Issue: 18 Pages: 9997-10003
  • DOI: 10.1128/jvi.00883-13
  • Peer Reviewed
• [Journal Article] Signal peptidase complex subunit 1 participates in the assembly of hepatitis C virus through an interaction with E2 and NS2 (2013)
  • Author(s): Suzuki R, Matsuda M, Watashi K, Aizaki H, Matsuura Y, Wakita T, Suzuki T
  • Journal Title: PLoS Pathog Volume: 9 Issue: 8 Pages: 1-12
  • DOI: 10.1371/journal.ppat.1003589
  • Peer Reviewed
• [Presentation] Host factors incolced in the propagation and pathogenesis of hepatitis C virus. (2014)
  • Author(s): Yoshiharu Matsuura, Toru Okamoto, Takasuke Fukuhara
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-09 – 2014-11-12
  • Invited
• [Presentation] Characterization of HCV propagation in miR-122 knockout cells (2014)
  • Author(s): Chikako Ono, Takasuke Fukuhara, Satomi Yamamoto, Masami Wada, Toru Okamoto, Daisuke Okuzaki, Yoshiharu Matsuura
  • Organizer: 第13回あわじしま感染症・免疫フォーラム
  • Place of Presentation: 奈良
  • Year and Date: 2014-09-23 – 2014-09-24
• [Presentation] Characterization of HCV Propagation in miR-122 Knockout Cells. (2014)
  • Author(s): Chikako Ono, Takasuke Fukuhara, Mai Shiokawa, Satomi Yamamoto, Masami Wada, Toru Okamoto, Daisuke Okuzaki, Yoshiharu Matsuura
  • Organizer: 33rd American Society for Virology, Annual Meeting
  • Place of Presentation: Colorado, USA
  • Year and Date: 2014-07-21 – 2014-07-25
• [Presentation] Role of HCV-RNA quasispecies on the cell-specific infectivity (2013)
  • Author(s): Takasuke Fukuhara, Satomi Yamamoto, Mai Shiokawa, Masami Wada, Chikako Ono, Toru Okamoto, Yoshiharu Matsuura
  • Organizer: 20th International Meeting on hepatitis C virus and related viruses
  • Place of Presentation: Melbourne
• [Presentation] Roles of de-ubiquitinating enzymes on the propagation of HCV (2013)
  • Author(s): Toru Okamoto, Yukari Sugiyama, Chikako Ono, Sayaka Aizawa, Pham Duc Ngoc, Takahisa Kohwaki, Eiji Hirooka, Takasuke Fukuhara, Masahiro Yamamoto, Yoshiharu Matsuura
  • Organizer: 20th International Meeting on hepatitis C virus and related viruses
  • Place of Presentation: Melbourne
• [Presentation] Propagation of HCV in the miR-122-knockout Huh7 cells (2013)
  • Author(s): Chikako Ono, Takasuke Fukuhara, Mai Shiokawa, Satomi Yamamoto, Masami Wada, Toru Okamoto, Daisuke Okuzaki, Yoshiharu Matsuura
  • Organizer: 20th International Meeting on hepatitis C virus and related viruses
  • Place of Presentation: Melbourne
• [Presentation] Role of HCV-RNA quasispecies on the cell-specific infectivity (2013)
  • Author(s): Takasuke Fukuhara, Satomi Yamamoto, Takashi Motomura, Mai Shiokawa, Chikako Ono, Hiroto Kambara, Toru Okamoto, Yoshiharu Matsuura
  • Organizer: 32nd American Society for Virology, Annual Meeting
  • Place of Presentation: Pennsylvania
• [Presentation] Innate immune response induced by baculovirus suppresses transgene expression (2013)
  • Author(s): Chikako Ono, Satomi Yamamoto, Akinori Ninomiya, Takasuke Fukuhara, Toru Okamoto, Takayuki Abe, and Yoshiharu Matsuura
  • Organizer: 32nd American Society for Virology, Annual Meeting
  • Place of Presentation: Pennsylvania
• [Presentation] Co-chaperones involved in the replication of hepatitis C virus. (2013)
  • Author(s): Okamoto T, Taguwa S, Moriishi K, Matsuura Y.
  • Organizer: Protein Homeostasis & Viral Infection: Mechanisms to Therapeutics.
  • Place of Presentation: Bethesda
  • Invited
• [Presentation] Host factors involved in HCV propagation. (2013)
  • Author(s): Matsuura Y.
  • Organizer: The 2013 Italy-Japan Liver Workshop “Hepatitis, Steatosis and Hepatocellular Carcinoma : molecular basis and clinical links”.
  • Place of Presentation: Marsala
• [Presentation] Host factors involved in the propagation and pathogenesis of hepatitis C virus. (2013)
  • Author(s): Matsuura Y.
  • Organizer: Infectious Diseases in Elderly Symposium.
  • Place of Presentation: Izmir
  • Invited
• [Presentation] Host factors involved in the propagation and pathogenesis of hepatitis C virus. (2013)
  • Author(s): Matsuura Y.
  • Organizer: The 3rd International Symposium on Infectious Disease and Signal Transduction and Taiwan-Japan Joint Symposium on Cell Signaling and Gene Regulation.
  • Place of Presentation: Tainan
  • Invited
• [Remarks] 大阪大学微生物病研究所分子ウイルス分野
  • URL: http://www-yoshi.biken.osaka-u.ac.jp
• [Remarks] 大阪大学微生物病研究所 分子ウイルス分野
  • URL: http://www-yoshi.biken.osaka-u.ac.jp