Study of mechanism for the development of ATL and HAM by using HTLV-1 infected humanized mouse model

• Project/Area Number: 21590515
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: Kansai Medical University
• Principal Investigator: FUJISAWA Jun-ichi 関西医科大学, 医学部, 教授 (40181341)
• Co-Investigator(Kenkyū-buntansha): TAKUNOUCHI Norihiro 関西医科大学, 医学部, 准教授 (20533235) ; TANAKA Masakazu 関西医科大学, 医学部, 助教 (20454613)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: HTLV-1 / ヒト化マウス / マウスモデル / ATL / NOG-SCID / HAM

Research Abstract

By infecting HTLV-1 to humanized NOG-SCID mouse established by the intra-bone-marrow transplantation of human hematopoietic stem cells we successfully recapitulated the ATL-like phenotypes such as overgrowth of infected T cells, hepatosplenomegaly and induction of T lymphocytes with flower-shaped nuclei. Host immune system against HTLV-1 was established and the outgrowth of limited number of infected T cell clones was observed. In the course of clonal selection of infected T cells the expression of HTLV-1 Tax became silenced and the infected CD25-negative T cells were changed to express CD25.

Research Products

• [Journal Article] The route of primary HTLV-1 infection regulates HTLV-1 distribution in reservoir organs of infected mice (2011)
  • Author(s): Tanaka M, Nitta T, Sun B, Fujisawa J, Miwa M
  • Journal Title: Exp. Thr. Med Volume: vol.2 Pages: 89-94
  • Peer Reviewed
• [Journal Article] Route of primary HTLV-1 infection regulates HTLV-1 distribution in reservoir organs of infected mice (2011)
  • Author(s): Tanaka M, Nitta T, Sun B, Fujisawa J, Miwa M
  • Journal Title: Exp.Thr.Med. Volume: 12 Issue: 1 Pages: 89-94
  • DOI: 10.3892/etm.2010.179
  • Peer Reviewed
• [Journal Article] Neuraminidase enhances the initial steps of human T-cell leukemia virus type 1 replication (2010)
  • Author(s): Tanaka M, Sun B, Tezuka K, Fujisawa J, Tanaka Y, Hoshino H, Miwa M
  • Journal Title: Microbes and Infection Volume: vol.12 Pages: 701-707
  • Peer Reviewed
• [Journal Article] Clonal proliferation of HTLV-1-infected cells is associated with spontaneous malignant tumor formation in mice (2009)
  • Author(s): Tanaka, M., T. Nitta, T. Yoshida, T. Konishi, Y. Kawazu, J. Fujisawa and M. Miwa
  • Journal Title: Int J Oncol Volume: vol.35 Pages: 119-125
  • Peer Reviewed
• [Journal Article] Involvement of TORC2, a CREB co-activator, in the in vivo-specific transcriptional control of HTLV-1 (2009)
  • Author(s): Jiang S, Inada T, Tanaka M, Furuta RA, Shingu K, Fujisawa J
  • Journal Title: Retrovirology Volume: vol.6 Pages: 73-73
  • Peer Reviewed
• [Journal Article] Clonal proliferation of HTLV-1-infected cells is associated with spontaneous malignant tumor formation in mice (2009)
  • Author(s): Tanaka, M., T.Nitta, T.Yoshida, T.Konishi, Y.Kawazu, J.Fujisawa, M.Miwa
  • Journal Title: Int J Oncol 35 Pages: 701-707
  • Peer Reviewed
• [Presentation] HTLV-1感染ヒト化マウスにおける欠損型プロウイルスの解析 (2011)
  • Author(s): 手塚健太、上野孝治、荀潤澤、竹之内徳博、田中正和、藤澤順一
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-05
• [Presentation] Anti-tumor effects of bovine lactoferrin to lymphoma cells expressing HTLV-1 Tax (2011)
  • Author(s): Masakazu Tanaka, Naoki Wada, Iwao Hashimoto, Sho Hasegawa, Hiroyuki Tsuda, Masanao Miwa, Jun-ichi Fujisawa
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-05
• [Presentation] Anti-tumor effects of bovine lactoferrin to lymphoma cells expressing HTLV-1 Tax (2011)
  • Author(s): 田中正和
  • Organizer: 第70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: 2011-10-05
• [Presentation] HTLV-1感染ヒト化マウスにおける欠損型プロウイルスの解析 (2011)
  • Author(s): 手塚健太
  • Organizer: 第70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: 2011-10-05
• [Presentation] Inverse correlation between tax and CD25 expressions in HTLV-1 infected CD4+T-cells in vivo (2011)
  • Author(s): Kenta Tezuka, Runze Xun, Mami Tei, Takaharu Ueno, Masakazu Tanaka, Norihiro Takenouchi, Jun-ichi Fujisawa
  • Organizer: The XV International Congress of Virology
  • Place of Presentation: 札幌
  • Year and Date: 2011-09-13
• [Presentation] Infection of defective virus correlated with the induction of CD25 positive CD4 T-cell during early phase of infection in humanized mouse model (2011)
  • Author(s): 上野孝治
  • Organizer: The XV International Congress of Virology
  • Place of Presentation: 札幌コンベンショナルセンター(札幌)
  • Year and Date: 2011-09-13
• [Presentation] Inverse correlation between tax and CD25 expressions in HTLV-1 infected CD4+ T-cells in vivo (2011)
  • Author(s): 手塚健太
  • Organizer: The XV International Congress of Virology
  • Place of Presentation: 札幌コンベンショナルセンター(札幌)
  • Year and Date: 2011-09-13
• [Presentation] Infection of defective virus correlated with the induction of CD25 positive CD4 T-cell during early phase of infection in humanized mouse model (2011)
  • Author(s): Takaharu Ueno, Kenta Tezuka, Runze Xun, Mami Tei, Masakazu Tanaka, Norihiro Takenouchi, Jun-ichi Fujisawa
  • Organizer: The XV International Congress of Virology
  • Place of Presentation: 札幌
  • Year and Date: 2011-09-12
• [Presentation] ATL-like overgrowth and clonal expansion of HTLV-1 infected CD25+CD4+T-lymphocyte in humanized-NOG mouse model (2011)
  • Author(s): Jun-ichi Fujisawa, Kenta Tezuka, Runze Xun, Mami Tei, Norihiro Takenouchi, Masakazu Tanaka
  • Organizer: 15th International conference on human retorovirology HTLV and related viruses
  • Place of Presentation: Leuven/Gembloux Belgium
  • Year and Date: 2011-06-05
• [Presentation] Inverse correlation between Tax anda CD25 expressions in HTLV-1 infected CD4 T-cells in vivo (2011)
  • Author(s): Kenta Tezuka, Runze Xun, Mami Tei, Takaharu Ueno, Masakazu Tanaka, Norihiro Takenouchi, Jun-ichi Fujisawa
  • Organizer: 15th International conference on human retorovirology HTLV and related viruses
  • Place of Presentation: Leuven/Gembloux Belgium
  • Year and Date: 2011-06-05
• [Presentation] ATL-like overgrowth and clonal expansion of HTLV-1 infected CD25+ CD4+ T-lymphocyte in humanized-NOG mouse model (2011)
  • Author(s): 藤澤順一
  • Organizer: 15th International conference on human retorovirology HTLV and related viruses
  • Place of Presentation: Leuven, Belgium
  • Year and Date: 2011-06-05
• [Presentation] Inverse correlation between Tax anda CD25 expressions in HTLV-1 infected CD4 T-cells in vivo (2011)
  • Author(s): 手塚健太
  • Organizer: 15th International conference on human retorovirology HTLV and related viruses
  • Place of Presentation: Leuven, Belgium
  • Year and Date: 2011-06-05
• [Presentation] HTLV-1感染ヒト化マウスを用いた感染T細胞選択過程の解析 (2010)
  • Author(s): 田中正和, 荀潤澤, 手塚健太, 三輪正直, 竹之内徳博, 藤澤順一
  • Organizer: 第58回日本ウイルス学会学術集会
  • Place of Presentation: 徳島
  • Year and Date: 2010-11-08
• [Presentation] HTLV-1感染ヒト化マウスを用いた感染T細胞選択過程の解析 (2010)
  • Author(s): 田中正和
  • Organizer: 第58回日本ウイルス学会学術集会
  • Place of Presentation: 徳島県郷土文化会館(徳島)
  • Year and Date: 2010-11-08
• [Presentation] HAM患者CD8陽性T細胞におけるTSLC1の発現抑制 (2010)
  • Author(s): 竹之内徳博
  • Organizer: 第58回日本ウイルス学会学術集会
  • Place of Presentation: 徳島県郷土文化会館(徳島)
  • Year and Date: 2010-11-08
• [Presentation] HTLV-1感染T細胞の浸潤能に与えるシアリダーゼの影響 (2010)
  • Author(s): 手塚健太
  • Organizer: 第58回日本ウイルス学会学術集会
  • Place of Presentation: 徳島県郷土文化会館(徳島)
  • Year and Date: 2010-11-08
• [Presentation] Immunotherapy for tumors using combination of allogenic intra-bone-marrow bone-marrow transplantation(IBM-BMT) and donor lymphocyte infusion(DLI) in EL4/Gax implanted mouse (2010)
  • Author(s): Tanaka M, Hasegawa S, Hashimoto I, Adachi Y, Ikehara S, Miwa M, Fujisawa J
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-22
• [Presentation] Immunotherapy for tumors using combination of allogenic intra-bone-marrow bone-marrow transplantation (IBM-BMT) and donor lymphocyte infusion (DLI) in EL4/Gax implanted mouse. (2010)
  • Author(s): 田中正和
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2010-09-22
• [Presentation] ヒト化マウスモデルにおけるHTLV-1感染CD25+T細胞のクローナル増殖 (2009)
  • Author(s): 手塚健太, 荀潤澤, 田中正和, 三輪正直, 竹之内徳博, 藤澤順一
  • Organizer: 第57回日本ウイルス学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2009-10-27
• [Presentation] HTLV-1感染ヒト化マウスT細胞におけるCD25の活性化 (2009)
  • Author(s): 荀潤澤, 手塚健太, 田中正和, 三輪正直, 竹之内徳博, 藤澤順一
  • Organizer: 第57回日本ウイルス学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2009-10-27
• [Presentation] ヒト化マウスモテルにおけるHTLV-1感染CD25陽性T細胞のクローナル増殖 (2009)
  • Author(s): 手塚健太
  • Organizer: 第57回 日本ウイルス学会学術集会
  • Place of Presentation: 都市センターホテル(東京)
  • Year and Date: 2009-10-27
• [Presentation] HTLV-1感染ヒト化マウスT細胞におけるCD25の活性化 (2009)
  • Author(s): 荀潤澤
  • Organizer: 第57回 日本ウイルス学会学術集会
  • Place of Presentation: 都市センターホテル(東京)
  • Year and Date: 2009-10-27
• [Presentation] マウスモデルを用いた骨髄移植/リンパ球輸注による抗ATL治療法の検討 (2009)
  • Author(s): 長谷川翔, 橋本岩雄, 田中正和, 足立靖, 池原進, 三輪正直, 藤澤順一
  • Organizer: 第57回日本ウイルス学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2009-10-26
• [Presentation] マウスモデルを用いた骨髄移植/リンパ球輸注による抗ATL治療法の検討 (2009)
  • Author(s): 長谷川翔
  • Organizer: 第57回 日本ウイルス学会学術集会
  • Place of Presentation: 都市センターホテル(東京)
  • Year and Date: 2009-10-26
• [Presentation] ヒト化マウスモデルにおけるHTLV-1感染CD4CD25陽性T細胞のクローナル増殖性とTax特異的なCTL検出について (2009)
  • Author(s): 田中正和, 荀潤澤, 手塚健太, 巽理恵, 竹之内徳博, 三輪正直, 藤澤順一
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-02
• [Presentation] Clonal expansion of HTLV-1 infected CD25^+ CD^4+T^- cells and the expression of Tax-specific CTLs in humanized mouse model (2009)
  • Author(s): 田中正和
  • Organizer: 第68回 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(横浜)
  • Year and Date: 2009-10-02
• [Remarks]
  • URL: http://www3.kmu.ac.jp/microbiol/
• [Remarks]
  • URL: http://www.kmu.ac.jp/graduate_school/2671t80000008f16.html
• [Remarks]
  • URL: http://www3.kmu.ac.jp/microbiol/
• [Remarks]
  • URL: http://www.kmu.ac.jp/graduate_school/2671t80000008f16.html
• [Remarks]
  • URL: http://www3.kmu.ac.jp/microbiol/
• [Remarks]
  • URL: http://www.kmu.ac.jp/graduate_school/2671t80000008f16.html
• [Remarks]
  • URL: http://www3.kmu.ac.jp/microbiol/