Study on the infection and proliferation of HCV during hepatic differentiation of human hepatic stem cells

• Project/Area Number: 24659205
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Virology
• Research Institution: Kyoto University
• Principal Investigator: HIJIKATA Makoto 京都大学, ウイルス研究所, 准教授 (90202275)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: ウイルス / 肝炎 / 肝幹細胞 / 肝分化 / 自然免疫 / インターフェロン / C型肝炎ウイルス / ヒト肝細胞 / 幹細胞 / 肝細胞分化 / ウイルス感染

Research Abstract

The aim of this study was to reveal the developmental stage of human hepatocytes permissive to the infection and proliferation of HCV, using human hepatic stem cells that originally established by our laboratory. Infection experiment of HCV using the hepatic stem cells after induction of hepatic differentiation suggested that the highly matured hepattocytes are required for efficient infection of HCV. Our results also suggested the requirement of suppression of innate immune system of the cells to establish efficient HCV culture system.

Research Products

• [Journal Article] Critical role of interferon-alpha constitutively produced in human hepatocytes in response to RNA virus infection (2014)
  • Author(s): Yoji Tsugawa, Hiroki Kato, Takashi Fujita, Kunitada Shimotohno, Makoto Hijikata
  • Journal Title: PLoS ONE Volume: 9
• [Journal Article] Critical role of interferon-α constitutively produced in human hepatocytes in response to RNA virus infection. (2014)
  • Author(s): Tsugawa Y, Kato H, Fujita T, Shimotohno K, Hijikata M.
  • Journal Title: PLoS One. Volume: 9 Issue: 2 Pages: e89869-e89869
  • DOI: 10.1371/journal.pone.0089869
  • Peer Reviewed / Open Access
• [Presentation] C型肝炎治療薬の新たな分子標的の探索 (2013)
  • Author(s): 土方誠
  • Organizer: 第13回肝疾患フォーラム学術集会基調講演
  • Place of Presentation: 大阪
  • Year and Date: 2013-11-09
  • Invited
• [Presentation] Type I and type III interferon play anti-viral roles cooperatively in human hepatocytes to prevent early infection spread of vitruses (2013)
  • Author(s): Yoji Tsugawa, Hiroki Kato, Takashi Fujita, Kunitada Shimotohno, Makoto Hijikata
  • Organizer: 20^<th> International symposium on hepatitis C virus and related viruses(6^<th>-10^<th>)
  • Place of Presentation: Melbourne, Australia
• [Presentation] ヒト肝細胞の抗ウイルス初期応答においてI型およびIII型インターフェロンは協調的に作用する (2013)
  • Author(s): 津川陽司、加藤博己、藤田尚志、下遠野邦忠、土方誠
  • Organizer: 第61回日本ウイルス学会学術集会
  • Place of Presentation: 神戸
• [Presentation] Type I and type III interferon play anti-viral roles cooperatively in human hepatocytes to prevent early infection spread of viruses. (2013)
  • Author(s): Tsugawa Y., Kato H., Fujita T., Shimotohno T., Hijikata M.
  • Organizer: 20th International symposium on hepatitis C virus and related viruses
  • Place of Presentation: Melbourne, Australia
• [Presentation] C型肝炎治療薬の新たな分子標的の探索 (2013)
  • Author(s): 土方誠
  • Organizer: 第13回肝疾患フォーラム学術集会 基調講演
  • Place of Presentation: 大阪
  • Invited
• [Remarks] 京都大学ウイルス研究所がんウイルス研究部門ヒトがんウイルス研究分野土方研究グループホームページ
  • URL: http://www.virus.kyoto-u.ac.jp/Lab/HCV/index.html
• [Remarks] 京都大学ウイルス研究所がんウイルス研究部門ヒトがんウイルス研究分野土方研究室
  • URL: http://www.virus.kyoto-u.ac.jp/Lab/HCV/index.html
• [Remarks] 京都大学ウイルス研究所がんウイルス研究部門ヒトがんウイルス研究分野土方研究室
  • URL: http://www.virus.kyoto-u.ac.jp/Lab/HCV2012/index.html