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Study on host factors involved in Hepatitis C virus life cycle

Research Project

Project/Area Number 23590104
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biological pharmacy
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

Fukasawa Masayoshi  国立感染症研究所, その他部局等, 室長 (20291130)

Project Period (FY) 2011-04-28 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
KeywordsHCV / cell muitants / C型肝炎ウイルス
Outline of Final Research Achievements

Life cycle of hepatitis C virus (HCV) is still poorly understood. In this project, I was trying to isolate host cell mutants resistant to HCV infection and to identify the defective genes in the mutants. A lot of hepatic cell mutants defective in HCV infection were established, and I found several novel host factors substantially involved in HCV infection. From the results of various analyses using established cell mutants defective in HCV infection, I also confirmed that a tight junction protein occludin is essential for both cell-free HCV entry and cell-to-cell HCV transmission in hepatic cells, and would be therefore a promising anti-HCV drug target.

Report

(6 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (30 results)

All 2016 2015 2014 2013 2012 2011

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Acknowledgement Compliant: 3 results,  Open Access: 3 results) Presentation (20 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 1 results)

  • [Journal Article] Occludin-Knockout Human Hepatic Huh7.5.1-8-Derived Cells Are Completely Resistant to Hepatitis C Virus Infection2016

    • Author(s)
      Yoshitaka Shirasago, Yoshimi Shimizu, Isei Tanida, Tetsuro Suzuki, Ryosuke Suzuki, Kazuo Sugiyama, Takaji Wakita, Kentaro Hanada, Kiyohito Yagi, Masuo Kondoh, and Masayoshi Fukasawa
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 39 Issue: 5 Pages: 839-848

    • DOI

      10.1248/bpb.b15-01023

    • NAID

      130005149248

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Monoclonal antibodies against extracellular domains of claudin-1 block hepatitis C virus infection in a mouse model2015

    • Author(s)
      Masayoshi Fukasawa, Shotaro Nagase, Yoshitaka Shirasago, Manami Iida, Mayo Yamashita, Kohki Endo, Kiyohito Yagi, Tetsuro Suzuki, Takaji Wakita, Kentaro Hanada, Hiroki Kuniyasu, Masuo Kondoh
    • Journal Title

      J Virol

      Volume: 89 Issue: 9 Pages: 4866-4879

    • DOI

      10.1128/jvi.03676-14

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Isolation and Characterization of an Huh.7.5.1-Derived Cell Clone Highly Permissive to Hepatitis C Virus2015

    • Author(s)
      Shirasago Y, Sekizuka T, Saito K, Suzuki T, Wakita T, Hanada K, Kuroda M, Abe R, Fukasawa M.
    • Journal Title

      Japanese Journal of Infectious Diseases

      Volume: 68 Issue: 2 Pages: 81-88

    • DOI

      10.7883/yoken.JJID.2014.231

    • NAID

      130004716751

    • ISSN
      1344-6304, 1884-2836
    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Targeting cellular squalene synthase, an enzyme essential for cholesterol biosynthesis is a potential antiviral strategy against hepatitis C virus2015

    • Author(s)
      Kyoko Saito, Yoshitaka Shirasago, Tetsuro Suzuki, Hideki Aizaki, Kentaro Hanada, Takaji Wakita, Masahiro Nishijima, Masayoshi Fukasawa
    • Journal Title

      J. Virol.

      Volume: 89 Issue: 4 Pages: 2220-2232

    • DOI

      10.1128/jvi.03385-14

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Retinoids and rexinoids inhibit hepatitis C virus independently of retinoid receptor signaling.2014

    • Author(s)
      Yuko Murakami, Masayoshi Fukasawa, Yukihiro Kaneko, Tetsuro Suzuki, Takaji Wakita, Hidesuke Fukazawa
    • Journal Title

      Microbes and Infection

      Volume: 16 Pages: 114-122

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] A class II phosphoinositide 3-kinase plays an indispensable role in hepatitis C virus replication2013

    • Author(s)
      Maehama T, Fukasawa M, Date T, Wakita T, Hanada K.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 440 Pages: 150-156

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Selective estrogen receptor modulators inhibit hepatitis C virus infection at multiple steps of the virus lifecycle2013

    • Author(s)
      Y. Murakami, M. Fukasawa, Y. Kaneko, T. Suzuki, T. Wakita, and H. Fukazawa
    • Journal Title

      Microbes and Infection

      Volume: 15 Pages: 45-55

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Establishment and characterization of occludin knock-out human hepatic Huh7.5.1 cells2015

    • Author(s)
      Yoshitaka Shirasago, Yoshimi Shimizu, Isei Tanida, Tetsuro Suzuki, Takaji Wakita, Kentaro Hanada, Kiyohito Yagi, Masuo Kondoh, and Masayoshi Fukasawa
    • Organizer
      The 22th International Symposium on Hepatitis C Virus and Related Viruses
    • Place of Presentation
      France
    • Year and Date
      2015-10-09
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒト肝臓由来培養細胞株からのOccludinノックアウト細胞株の樹立と本細胞株を用いたHCV感染の解析2015

    • Author(s)
      白砂圭崇、清水芳実、谷田以誠、鈴木哲朗、脇田隆字、花田賢太郎、近藤昌夫、八木清仁、深澤征義
    • Organizer
      第22回肝細胞研究会
    • Place of Presentation
      米子
    • Year and Date
      2015-06-04
    • Related Report
      2015 Annual Research Report
  • [Presentation] HCVに対して高感染感受性を有するHuh7.5.1細胞亜株の樹立と性状解析2014

    • Author(s)
      白砂 圭崇、関塚剛史、齊藤恭子、鈴木哲朗、脇田隆字、花田賢太郎、黒田誠、安部良、深澤征義
    • Organizer
      第62回日本ウイルス学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-10 – 2014-11-12
    • Related Report
      2014 Research-status Report
  • [Presentation] Development of claudin-1-specific ligand2013

    • Author(s)
      Shotaro Nagase, Mayo Yamashita, Manami Iida, Akihiro Watari, Masuo Kondoh, Masayoshi Fukasawa, Kiyohito Yagi
    • Organizer
      Experimental Biology 2013
    • Place of Presentation
      Boston, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] 上皮細胞を標的とした創薬基盤研究第1報~claudin-1特異性抗体の創製~2013

    • Author(s)
      長瀬翔太郎、山下真代、飯田愛未、渡利彰浩、近藤昌夫、深澤征義、多田稔、石井明子、八木清仁
    • Organizer
      第29回日本DDS学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
  • [Presentation] 上皮細胞を標的とした創薬基盤研究第2報~claudin-1抗体のC型肝炎治療への応用~2013

    • Author(s)
      飯田愛未、長瀬翔太郎、山下真代、近藤昌夫、八木清仁、國安弘基、深澤征義
    • Organizer
      第29回日本DDS学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
  • [Presentation] Claudin-1-specific monoclonal antibodies and their inhibition of hepatitis C virus infection2013

    • Author(s)
      Shotaro Nagase, Mayo Yamashita, Manami Iida, Akihiro Watari, Kiyohito Yagi, Masayoshi Fukasawa, Masuo Kondoh
    • Organizer
      40th Annual Meeting & Exposition of the Controlled Release Society
    • Place of Presentation
      Honolulu, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Claudin 1抗体の樹立と本抗体によるC型肝炎ウイルス感染阻害2013

    • Author(s)
      深澤征義、白砂圭崇、長瀬翔太郎、近藤昌夫、八木清仁、安部 良、花田賢太郎
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] C型肝炎ウイルスへの感染感受性を欠損した宿主肝細胞変異株の分離と性状解析2013

    • Author(s)
      白砂圭崇、鈴木哲朗、脇田隆字、花田賢太郎、安部良、深澤征義
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] Inhibition of hepatitis C virus infection by mouse anti-claudin 1 monoclonal antibodies2013

    • Author(s)
      Masayoshi Fukasawa, Shotaro Nagase, Mayo Yamashita, Manami Iida, Yoshitaka Shirasago, Akihiro Watari, Tetsuro Suzuki, Takaji Wakita, Kiyohito Yagi, Masuo Kondoh
    • Organizer
      The 20th International Symposium on Hepatitis C Virus and Related Viruses
    • Place of Presentation
      Melbourne, Australia
    • Related Report
      2013 Research-status Report
  • [Presentation] Development of claudin-1 monoclonal antibodies and their pharmaceutical activities2013

    • Author(s)
      Mayo Yamashita, Shotaro Nagase, Manami Iida, Yoshitaka Shirasago, Masayoshi Fukasawa, Masuo Kondoh, Minoru Tada, Akiko Ishii, Akihiro Watari, Kiyohito Yagi
    • Organizer
      日本薬物動態学会第28回年会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] 宿主Claudin 1―ウイルス相互作用を標的としたC型肝炎ウイルス感染阻害2013

    • Author(s)
      深澤征義、近藤昌夫、長瀬翔太郎、白砂圭崇、飯田愛未、山下真代、鈴木哲朗、脇田隆字、八木清仁、安部 良、花田賢太郎
    • Organizer
      第61回日本ウイルス学会学術集会
    • Place of Presentation
      神戸
    • Related Report
      2013 Research-status Report
  • [Presentation] Huh7.5.1細胞由来C型肝炎ウイルス非感染感受性変異株の分離と性状解析2013

    • Author(s)
      白砂圭崇、鈴木哲朗、脇田隆字、花田賢太郎、安部良、深澤征義
    • Organizer
      第61回日本ウイルス学会学術集会
    • Place of Presentation
      神戸
    • Related Report
      2013 Research-status Report
  • [Presentation] In vitro and in vivo inhibition of hepatitis C virus infection by mouse anti-human claudin 1 monoclonal antibodies2013

    • Author(s)
      Masayoshi Fukasawa, Shotaro Nagase, Mayo Yamashita, Kentaro Hanada, Akihiro Watari, Kiyohito Yagi, Masuo Kondoh
    • Organizer
      The 2013 ASCB Annual Meeting
    • Place of Presentation
      New Orleans, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Claudin 1を標的としたC型肝炎ウイルス感染阻害2013

    • Author(s)
      深澤征義
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Claudinを標的とした創薬基盤技術の開発第1報~claudin-1特異的binderの創製~2013

    • Author(s)
      長瀬翔太郎、山下真代、飯田愛未、渡利彰浩、近藤昌夫、深澤征義、八木清仁
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] 高感染能を有する2a型C型肝炎ウイルスJFH-1由来変異株の性状解析2013

    • Author(s)
      白砂圭崇、齊藤 恭子 、村上 裕子、 深澤 秀輔 、鈴木 哲朗、脇田 隆字、花田 賢太郎 、千葉 丈、安部 良、深澤 征義
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] Isolation and characterization of a mutant hepatitis C virus adapted to mouse CD812012

    • Author(s)
      Masayoshi Fukasawa, Ryo Anai, Yoshitaka Shirasago, Kyoko Saito, Yuko Murakami, Hidesuke Fukazawa, Tetsuro Suzuki, Takaji Wakita, Jo Chiba, Kentaro Hanada
    • Organizer
      The 19th International Symposium on Hepatitis C Virus and Related Viruses
    • Place of Presentation
      Italy
    • Related Report
      2012 Research-status Report
  • [Presentation] 高感染能を有するHCV JFH-1適応変異株の性状解析2012

    • Author(s)
      白砂圭崇、齋藤恭子、村上 裕子、深澤 秀輔、 鈴木 哲朗、 脇田 隆字、花田 賢太郎、 千葉 丈、安部 良、深澤 征義
    • Organizer
      第60回日本ウイルス学会学術集会
    • Place of Presentation
      大阪
    • Related Report
      2012 Research-status Report
  • [Presentation] 適応変異を有する高感染性HCV株の分離2011

    • Author(s)
      深澤征義、白砂圭崇、齋藤恭子、村上裕子、深澤秀輔、鈴木哲朗、鈴木亮介、脇田隆字、千葉丈
    • Organizer
      第18回HCVおよび関連ウイルスに関する国際会議
    • Place of Presentation
      Seattle, USA
    • Related Report
      2011 Research-status Report
  • [Patent(Industrial Property Rights)] 抗体、フラグメント及び抗HCV治療剤2013

    • Inventor(s)
      近藤昌夫、深澤征義、石井明子、多田稔、八木清仁、渡利彰浩
    • Industrial Property Rights Holder
      大阪大学・ヒューマンサイエンス振興財団
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-11-08
    • Related Report
      2013 Research-status Report
    • Overseas
  • [Patent(Industrial Property Rights)] 抗体、フラグメント、分子及び抗HCV治療剤2013

    • Inventor(s)
      近藤昌夫、深澤征義、石井明子、多田稔、八木清仁、渡利彰浩
    • Industrial Property Rights Holder
      大阪大学・ヒューマンサイエンス振興財団
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-02-28
    • Related Report
      2012 Research-status Report
  • [Patent(Industrial Property Rights)] 培養細胞、及び、細胞構築方法2012

    • Inventor(s)
      深澤征義、花田賢太郎
    • Industrial Property Rights Holder
      ヒューマンサイエンス振興財団
    • Industrial Property Rights Type
      特許
    • Filing Date
      2012-07-10
    • Related Report
      2012 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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