Development ofan assay system for hepatitis C virus in mice

2012 Fiscal Year Final Research Report

• Project/Area Number: 23659039
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Osaka University
• Principal Investigator: KONDOH Masuo 大阪大学, 薬学研究科(研究院), 准教授 (50309697)
• Project Period (FY): 2011 – 2012
• Keywords: C 型肝炎 / アデノウイルス / RNA pol I 系

Research Abstract

Host tropism of hepatitis C virus (HCV) is limited to human andchimpanzee. HCV infection has never been fully understood because there are few conventional models for HCV infection. The efficient delivery of the HCV RNA sub-genomic replicon into cells is useful for basic and pharmaceutical studies. The adenovirus (Ad) vector is a convenient and efficient tool for the transduction of foreign genes into cellsin vitro and in vivo. However, an Ad vector expressing the HCV replicon has never been developed. In the present study, we developed Ad vector containing an RNA polymerase (pol) I-dependent expression cassette and a tetracycline-controllable RNA pol I-dependent expression system. We prepared a hybrid promoter from the tetracycline-responsive element and the RNA pol I promoter. Ad vector particles coding the hybrid promoter-drivenHCV replicon could be amplified, and interferon, an inhibitor of HCV replication, reduced HCV replication in cells transduced with the Ad vector coding HCV replicon. These results indicate that the Ad vector system is useful for HCV research.

Research Products

• [Journal Article] Development of an adenovirus vector containing a hepatitis C virus expression cassette and its application (2013)
  • Author(s): Takeshi Yoshida, Masuo Kondoh, Hiroyuki Mizuguchi, Kiyohito Yagi
  • Journal Title: Yakugakuzasshi Volume: 133 Pages: 305-311
• [Journal Article] New approaches to drug discovery research and medical treatment using viruses-Viruses are valuable materials- (2013)
  • Author(s): Fuminori Sakurai, Masuo Kondoh
  • Journal Title: Yakugakuzasshi Volume: 133 Pages: 289
• [Journal Article] Suppression of hepatitis C virus replicon by adenovirus vector-mediated expression of tough decoy RNA against miR-122a (2012)
  • Author(s): Fuminori Sakurai, Norihisa Furukawa, Maiko Higuchi, Sayuri Okamoto, Kaori Ono, Takeshi Yoshida, Masuo Kondoh, Kiyohito Yagi, Naoya Sakamoto, Kazufumi Katayama, Hiroyuki Mizuguchi
  • Journal Title: Virus Res Volume: 165 Pages: 214-218
• [Journal Article] Promising targets for anti-hepatitis C virus agents (2011)
  • Author(s): Takeshi Yoshida, Masuo Kondoh, Kiyohito Yagi
  • Journal Title: Curr Med Chem Volume: 18 Pages: 1239-1244
• [Journal Article] Use of human hepatocyte-like cells derived from induced pluripotent stem cells as a model for hepatocytes in hepatitis C virus infection (2011)
  • Author(s): Takeshi Yoshida, Kazuo Takayama, Masuo Kondoh, Fuminori Sakurai, Hideki Tani, Naoya Sakamoto, Yoshiharu Matsuura, Hiroyuki Mizuguchi, Kiyohito Yagi
  • Journal Title: Biochem Biophys Res Commun Volume: 416 Pages: 119-124
• [Journal Article] Adenovirus vector-mediated assay system for Hepatitis C virus replication (2011)
  • Author(s): Takeshi Yoshida, Masuo Kondoh, Manabu Ojima, Hiroyuki Mizuguchi, Yoshiaki Yamagishi, Naoya Sakamoto, Kiyohito Yagi
  • Journal Title: Nucleic Acid Res Volume: 39 Pages: e64
• [Presentation] Evaluation of HCV infection and replication using human iPS cell-derived hepatocytes (2012)
  • Author(s): Kiyohito Yagi, Takeshi Yoshida, Seiji Yamane, Kazuo Takayama, Akihiro Watari, Masuo Kondoh, Fuminori Sakurai, Naoya Sakamoto, Yoshiharu Matsuura, Hiroyuki Mizuguchi
  • Organizer: 19thInternational Symposium on Hepatittis C virus and Relate viruses 2012
  • Place of Presentation: Venice, Italy
  • Year and Date: 20121005-09
• [Presentation] Human iPS-derived hepatocyte-like cells as a model for hepatitis C virus infection (2012)
  • Author(s): Seiji Yamane, Takeshi Yoshida, Kazuo Takayama, Masuo Kondoh, Fuminori Sakurai, Hiroyuki Mizuguchi, Kiyohito Yagi
  • Organizer: Experimental Biology 2012
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 20120421-25
• [Presentation] ヒト iPS 細胞由来肝細胞を用いた HCV 感染モデルの作製 (2012)
  • Author(s): 山根誠司、吉田孟史、高山和雄、近藤昌夫、桜井文教、谷英樹、坂本直哉、松浦善治、水口裕之、八木清仁
  • Organizer: 日本薬学会第132 年会
  • Place of Presentation: 札幌
  • Year and Date: 20120328-31
• [Presentation] アデノウイルスベクターを利用した C 型肝炎研究の新展開 (2012)
  • Author(s): 近藤昌夫、水口裕之、八木清仁
  • Organizer: 日本薬学会第132 年会
  • Place of Presentation: 札幌
  • Year and Date: 20120328-31
• [Presentation] Development of an RNA polymerase I-driven adenoviral vector and its application in an HCV replication assay (2011)
  • Author(s): Takeshi Yoshida, Fumi Satoh, Akihito Watari, Masuo Kondoh, Hiroyuki Mizuguchi, Naoya Sakamoto, Kiyohito Yagi
  • Organizer: 18thInternational Symposium of hepatitis C virus and related viruses
  • Place of Presentation: Seattle, WA, USA
  • Year and Date: 20110908-12
• [Presentation] RNA ポリメラーゼ I 発現系を利用した長鎖 RNA 発現ベクターの開発 (2011)
  • Author(s): 吉田孟史、佐藤芙美、渡利彰浩、近藤昌夫、水口裕之、八木清仁
  • Organizer: 第27回日本DDS 学会
  • Place of Presentation: 東京
  • Year and Date: 20110609-10
• [Presentation] Development of RNA pol-driven adenovirus vector expressing hepatitis C virus replicon (2011)
  • Author(s): Masuo Kondoh, Yoshiaki Yamagishi, Takeshi Yoshida, Hiroyuki Mizuguchi, Naoya Sakamoto, Akihiro Watari, Kiyohito Yagi
  • Organizer: Experimental Biology 2011
  • Place of Presentation: Washington, DC, USA
  • Year and Date: 20110404-13