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Analysis of factors involved in the establishment of asymptomatic carrier state in HTLV-1 infected humanized mice

Research Project

Project/Area Number 15K08506
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Virology
Research InstitutionKansai Medical University

Principal Investigator

FUJISAWA Jun-ichi  関西医科大学, 医学部, 教授 (40181341)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsHTLV-1 / ATL / ヒト化マウス / Tax / HBZ / HTLV-1 / マウスモデル / Tax
Outline of Final Research Achievements

In the course of HTLV-1 infection in humanized mouse, highly-Tax-expressing infected-T-cell clones expanded preferentially in the first four weeks of infection but subsequently were reduced provably due to the induction of cytotoxic T-lymphocytes against Tax in the later period. Instead, after eight weeks post infection, infected clones were composed of T-cells expressing larger amount of HBZ most likely because of reverse orientation of the provirus integration to the direction of host gene transcription in the introns. Thus, the elimination of Tax-expressing clones and the selective growth of HBZ expressing clones are suggested to be a major factor to sustain the slow growth of infected cells to establish the asymptomatic carrier state of infection.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (26 results)

All 2017 2016 2015 Other

All Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (17 results) (of which Int'l Joint Research: 6 results) Book (1 results) Remarks (3 results)

  • [Journal Article] Human T-cell leukemia virus type 1 infects multiple lineage hematopoietic cells in vivo2017

    • Author(s)
      Furuta Rie、Yasunaga Jun-ichirou、Miura Michi、Sugata Kenji、Saito Akatsuki、Akari Hirofumi、Ueno Takaharu、Takenouchi Norihiro、Fujisawa Jun-ichi、Koh Ki-Ryang、Higuchi Yusuke、Mahgoub Mohamed、Shimizu Masakazu、Matsuda Fumihiko、Melamed Anat、Bangham Charles R.、Matsuoka Masao
    • Journal Title

      PLOS Pathogens

      Volume: 13 Issue: 11 Pages: 1-22

    • DOI

      10.1371/journal.ppat.1006722

    • NAID

      120006697285

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Potential role of heme metabolism in the inducible expression of heme oxygenase-12017

    • Author(s)
      Taka-aki Takeda, Machiko Sasai, Yuka Adachi, Keiko Ohnishi, Jun-ichi Fujisawa, Shingo Izawa, Shigeru Taketani
    • Journal Title

      Biochem. Biophys. Acta

      Volume: 1876 Issue: 7 Pages: 1813-1824

    • DOI

      10.1016/j.bbagen.2017.03.018

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Poly(ADP-ribose). Structure, Physicochemical Properties and Quantification in vivo, with special reference to poly(ADP-ribose) binding protein modules2016

    • Author(s)
      Miwa M, Ida C, Yamashita S, Tanaka M, Fujisawa J
    • Journal Title

      Current Protein and Peptide Science

      Volume: 17 Pages: 683-692

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tax peptide vaccine suppressed the leukemia in humanized mouse2015

    • Author(s)
      Jun-ichi Fujisawa, Sung-il Lee, Jinchun Yao, Yihua Ren, Masakazu Tanaka
    • Journal Title

      Retrovirology

      Volume: 12(Suppl1) Issue: S1

    • DOI

      10.1186/1742-4690-12-s1-o43

    • Related Report
      2015 Research-status Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Induction of APOBEC3B cytidine deaminase gene in HTLV-1 infected T-cells of ATL model mouse2015

    • Author(s)
      Masakazu Tanaka, Jinchun Yao, Sung-il Lee, Yihua Ren, Norihiro Takenouchi, Jun-ichi Fujisawa
    • Journal Title

      Retrovirology

      Volume: 12(Suppl1) Issue: S1 Pages: 043-043

    • DOI

      10.1186/1742-4690-12-s1-p11

    • Related Report
      2015 Research-status Report
    • Open Access / Int'l Joint Research
  • [Presentation] Both HBZ Protein and mRNA are Required for Leukemic Growth of HTLV-l-infected T-cells in Humanized Mouse Model2017

    • Author(s)
      Ancy Joseph, Takaharu Ueno, Yihua Ren, Jinchun Yaol,Sung-il Lee, Masakazu Tanaka, Jun-ichi Fujisawa
    • Organizer
      18th International Conference on Human Retrovirology
    • Place of Presentation
      ホテルグランドアーク半蔵門(東京)
    • Year and Date
      2017-03-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effect of Adjuvant in the Tax Vaccination of Humanized Mouse to Prevent HTLV-l Infection2017

    • Author(s)
      Masakazu Tanaka, Yihua Ren, Jinchun Yao, Sung-il Lee, Norihiro Takenouchi, Jun-ichi Fujisawa
    • Organizer
      18th International Conference on Human Retrovirology
    • Place of Presentation
      ホテルグランドアーク半蔵門(東京)
    • Year and Date
      2017-03-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Establishment of an in vitro HTLV-l Infection Model Via Dendritic Cells2017

    • Author(s)
      Norihiro Takenouchi, Masakazu Tanaka, Jun-ichi Fujisawa
    • Organizer
      18th International Conference on Human Retrovirology
    • Place of Presentation
      ホテルグランドアーク半蔵門(東京)
    • Year and Date
      2017-03-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] HTlV-l Infection in Multiple lineages of Hematopoietic Cells2017

    • Author(s)
      Rie Furuta, Jun-ichirou Yasunaga, Michi Miura, Kenji Sugata, Akatsuki Saito, Hirofumi Akari, Takaharu Ueno, Norihiro Takenouchi, Jun-ichi Fujisawa, Ki-Ryang Koh, Masakazu Shimizu, Fumihiko Matsuda , Anat Melamed, Charles R Bangham, Masao Matsuoka
    • Organizer
      18th International Conference on Human Retrovirology
    • Place of Presentation
      ホテルグランドアーク半蔵門(東京)
    • Year and Date
      2017-03-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 抗HTLV-1抗体によるHTLV-1感染の活性化2017

    • Author(s)
      西川瑞希、大村裕樹、上野孝治、田中勇悦、藤澤順一
    • Organizer
      第4回日本HTLV-1学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 標的細胞との細胞接着による感染細胞プロウイルスの活性化2017

    • Author(s)
      大村裕樹、西川瑞希、Ancy Joseph、上野孝治、藤澤順一
    • Organizer
      第4回日本HTLV-1学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒト化マウスを用いたHTLV-1感染予防ワクチンにおけるアジュバント効果の組織病理学的検討2017

    • Author(s)
      田中正和、 福原貴太郎、竹之内徳博、任翊華、姚錦春、李成一、植田祥啓、木梨達雄、藤澤順一
    • Organizer
      第4回日本HTLV-1学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Effects of Tax vaccine adjuvants in HTLV-1 humanized mice2017

    • Author(s)
      Masakazu Tanaka, Takataro Fukuhara, Sung-il Lee, Yihua Ren, Jinchun Yao, Norihiro Takenouchi, Yoshihiro Ueda, Tatsuo Kinashi, Jun-ichi Fujisawa
    • Organizer
      第76回日本癌学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Analysis of HBZ gene product function in HTLV-1 infected mouse model2017

    • Author(s)
      Takaharu Ueno、Ancy Joseph、Yuihua Ren、Jinchun Yao、Sung-Il Lee、Masakazu Tanaka Jun-ichi Fujisawa
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ATL 発症過程における感染細胞内Tax 遺伝子発現の変動2016

    • Author(s)
      任 翊華、田中正和、姚 錦春、李 成一、藤澤順一
    • Organizer
      第3回日本HTLV学会学術集会
    • Place of Presentation
      鹿児島県県市町村自治会館(鹿児島)
    • Year and Date
      2016-08-26
    • Related Report
      2016 Research-status Report
  • [Presentation] Establishment of HTLV-1 infected Jurkat cell lines with mutated Tax and HBZ genes2016

    • Author(s)
      Ancy Joseph 、Takaharu Ueno、Jun-ichi Fujisawa
    • Organizer
      第3回日本HTLV学会学術集会
    • Place of Presentation
      鹿児島県県市町村自治会館(鹿児島)
    • Year and Date
      2016-08-26
    • Related Report
      2016 Research-status Report
  • [Presentation] HTLV-1 感染ヒ卜化マウスを用いた感染予防ワクチンにおけるアジュバント効果の検討2016

    • Author(s)
      田中正和、任 翊華、竹之内徳博、姚 錦春、李 成一、藤澤順一
    • Organizer
      第3回日本HTLV学会学術集会
    • Place of Presentation
      鹿児島県県市町村自治会館(鹿児島)
    • Year and Date
      2016-08-26
    • Related Report
      2016 Research-status Report
  • [Presentation] 血液系細胞におけるHTLV-1 感染とその意義2016

    • Author(s)
      古田梨愛、安永純一朗、三浦未知、菅田謙治、齋藤暁、明里宏文、上野孝治、竹之内徳博、藤澤順一、清水正和、松田文彦、Melamed Anat、Charles Bangham、松岡雅雄
    • Organizer
      第3回日本HTLV学会学術集会
    • Place of Presentation
      鹿児島県県市町村自治会館(鹿児島)
    • Year and Date
      2016-08-26
    • Related Report
      2016 Research-status Report
  • [Presentation] Induction of APOBEC3B cytidine deaminase gene in HTLV-1 infected T-cells of ATL model mouse2015

    • Author(s)
      Masakazu Tanaka, Jinchun Yao, Sung-il Lee, Yihua Ren, Norihiro Takenouchi, Jun-ichi Fujisawa
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場、名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] HTLV-1感染ヒト化マウスにおけるシチジンデアミナーゼAPOBEC3B遺伝子の活性化2015

    • Author(s)
      田中正和、姚錦春、李成一、任翊華、竹之内徳博、藤澤順一
    • Organizer
      第2回日本 HTLV-1学会学術集会
    • Place of Presentation
      東京大学医科学研究所講堂、東京
    • Year and Date
      2015-08-21
    • Related Report
      2015 Research-status Report
  • [Presentation] Tax peptide vaccine suppressed the leukemia in humanized mouse2015

    • Author(s)
      Jun-ichi Fujisawa, Sung-il Lee, Jinchun Yao, Yihua Ren, Masakazu Tanaka
    • Organizer
      7th Conference on Human Retroviruses: HTLV and Related Viruses
    • Place of Presentation
      Trois Ilets, Martinique
    • Year and Date
      2015-06-18
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Induction of APOBEC3B cytidine deaminase gene in HTLV-1 infected T-cells of ATL model mouse2015

    • Author(s)
      Masakazu Tanaka, Jinchun Yao, Sung-il Lee, Yihua Ren, Norihiro Takenouchi, Jun-ichi Fujisawa
    • Organizer
      7th Conference on Human Retroviruses: HTLV and Related Viruses
    • Place of Presentation
      Trois Ilets, Martinique
    • Year and Date
      2015-06-18
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Book] Adult T-cell Leukemia/Lymphoma2017

    • Author(s)
      Jun-ichi Fujisawa
    • Publisher
      Springer Japan KK
    • ISBN
      9784431565215
    • Related Report
      2017 Annual Research Report
  • [Remarks] 関西医科大学 微生物学講座

    • URL

      http://www3.kmu.ac.jp/microbiol/KMU_Microbiology/Top.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] 関西医科大学 医学部 学部・大学院 微生物学

    • URL

      http://www.kmu.ac.jp/faculty/medical/category2/unit8.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] 関西医科大学微生物学講座ホームページ

    • URL

      http://www3.kmu.ac.jp/microbiol/KMU_Microbiology/Top.html

    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

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