Development of HTLV-1 carrier model mice aming for preventing ATL development

• Project/Area Number: 15K09462
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Hamaguchi Isao 国立感染症研究所, 血液・安全性研究部, 部長 (90348780)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: HTLV-1 / ヒト化マウス / キャリア / モデルマウス / 免疫不全マウス / 経口感染 / 潜伏感染

Outline of Final Research Achievements

We developed humanized mice by using NOJ (NOD/SCID/JAK3 KO) mice. Human hematopoietic stem cells were transplanted into neonatal liver of NOJ mice, HTLV-1 infected cells are administrated through the humanized mice oral. The mice were infected by HTLV-1, and we could analyze the infectious mechanism of HTLV-1 for the long periods.
Furthermore, we have developed new immunodeficient mice with HLA-A*02:01 gene (NOG-HLA-A2 Tg). Hematopoietic stem cells that contained HLA-A*02:01 were transplanted into the humanized mice. These mice would be appropriate for extrapolation to human HTLV-1 carrier.

Research Products

• [Journal Article] Control of Human T-Cell Leukemia Virus Type 1 (HTLV-1) Infection by Eliminating Envelope Protein-Positive Cells with Recombinant Vesicular Stomatitis Viruses Encoding HTLV-1 Primary Receptor. (2018)
  • Author(s): Tezuka K, Okuma K, Kuramitsu M, Matsuoka S, Tanaka R, Tanaka Y, Hamaguchi I.
  • Journal Title: Journal of Virology Volume: 92(4) Issue: 4
  • DOI: 10.1128/jvi.01885-17
  • Peer Reviewed / Open Access
• [Journal Article] A novel neuropilin-1 binding sequence in the human T-cell lymphotropic virus type 1 envelope glycoprotein (2018)
  • Author(s): Kusunoki H, Tanaka T, Kohno T, Matsuhashi K, Hosoda K, Wakamatsu K, Hamaguchi I
  • Journal Title: Biochim Biophys Acta Volume: 1866 Issue: 4 Pages: 541-548
  • DOI: 10.1016/j.bbapap.2018.02.003
  • Peer Reviewed
• [Journal Article] Proviral features of human T cell leukemia virus type 1 in carriers with indeterminate western blot analysis results. (2017)
  • Author(s): Kuramitsu M, Sekizuka T, Yamochi T, Firouzi S, Sato T, Umeki K, Sasaki D, Hasegawa H, Kubota R, Sobata R, Matsumoto C, Kaneko N, Momose H, Araki K, Saito M, Nosaka K, Utsunomiya A, Koh K, Ogata M, Uchimaru K, Iwanaga M, Sagara Y, Yamano Y, et al.
  • Journal Title: J Clin Microbiol. Volume: 55(9) Issue: 9 Pages: 2838-2849
  • DOI: 10.1128/jcm.00659-17
  • Peer Reviewed / Open Access
• [Journal Article] Incidence of new HTLV-1 infections among adolescents and adults in Japan: a nationwide retrospective cohort analysis of repeat blood donors. (2016)
  • Author(s): Satake M, Iwanaga M, Sagara Y, Watanabe T, Okuma K, Hamaguchi I
  • Journal Title: Lancet Infect Dis Volume: 16 Issue: 11 Pages: 1246-1254
  • DOI: 10.1016/s1473-3099(16)30252-3
  • Peer Reviewed
• [Journal Article] Impact of the SCF signaling pathway on leukemia stem cell-mediated ATL initiation and progression in an HBZ transgenic mouse model. (2016)
  • Author(s): Kuribayashi W, Takizawa K, Sugata K, Kuramitsu M, Momose H, Sasaki E, Hiradate Y, Furuhata K, Asada Y, Iwama A, Matsuoka M, Mizukami T*, Hamaguchi I*.
  • Journal Title: Oncotarget Volume: 7(32) Issue: 32 Pages: 51027-51043
  • DOI: 10.18632/oncotarget.10210
  • Peer Reviewed / Open Access
• [Journal Article] Furin-dependent CCL17-fused recombinant toxin controls HTLV-1 infection by targeting and eliminating infected CCR4-expressing cells in vitro and in vivo. (2015)
  • Author(s): Okuma K, Hiyoshi M, Tateyama S, Takizawa K, Saito M, Kuramitsu M, Araki K, Morishita K, Okada S, Yamamoto N, Biragyn A, Yamaguchi K, Hamaguchi I.
  • Journal Title: Retrovirology Volume: 12 Issue: 1 Pages: 1-14
  • DOI: 10.1186/s12977-015-0199-8
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Standardization of quantitative PCR for human T-cell leukemia virus type 1 in Japan: A collaborative study (2015)
  • Author(s): Kuramitsu M, Okuma K, Yamochi T. et al
  • Journal Title: J. Clin. Microbien. Volume: 53 Issue: 11 Pages: 3485-3491
  • DOI: 10.1128/jcm.01628-15
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Targeting and Eliminating HTLV-1-infected Cells with Cytolytic Recombinant Vesicular Stomatitis Viruses Encoding HTLV-1 Primary Receptor (2017)
  • Author(s): Kenta Tezuka, Kazu Okuma, Madoka Kuramitsu, Yuetsu Tanaka, Reiko Tanaka, Isao Hamaguchi
  • Organizer: 18th International Conference on Human Retrovirology: HTLV and Related Viruses
  • Place of Presentation: 東京
  • Year and Date: 2017-03-07
• [Presentation] HTLV-1受容体をコードする組換え水疱性口内炎ウイルスを用いたHTLV-1感染の制御 (2017)
  • Author(s): 手塚健太、大隈和、倉光球、田中勇悦、田中礼子、浜口功
  • Organizer: 日本HTLV-1学会
• [Presentation] The c-kit-SCF signaling in the leukemic stem cells development and differentiation in ATL model mice (2015)
  • Author(s): Kuribayashi W, Mizukami T, Takizawa K, Sugata K, Kuramitsu M, Kojima K, Momose H, Asada Y, Iwama A, Matsuoka M, Hamaguchi I
  • Organizer: 日本血液学会
  • Place of Presentation: 金沢
  • Year and Date: 2015-10-16
• [Patent(Industrial Property Rights)] 組換え水疱性口内炎ウイルスを用いたワクチン・治療薬開発に向けたモニタリングのためのウイルスベクター定量法 (2017)
  • Inventor(s): 手塚健太、大隈和、浜口功
  • Industrial Property Rights Holder: 手塚健太、大隈和、浜口功
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2017-131361
  • Filing Date: 2017