2021 Fiscal Year Final Research Report
Development of the next-generation humanized mouse model for HTLV-1 infection
| Project/Area Number |
19K16032
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 42040:Laboratory animal science-related
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
TEZUKA Kenta 国立感染症研究所, 血液・安全性研究部, 主任研究官 (10754533)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | HTLV-1感染症 / 次世代ヒト化マウス / Tax特異的CTL / HLA-A*02:01遺伝子 / 潜伏感染 |
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| Outline of Final Research Achievements |
In this study, we aimed to establish a humanized mouse model of HTLV-1 infection that recapitulates human immune responsiveness using next-generation humanized mice transduced with HLA molecules. Induction of HLA-restricted HTLV-1 Tax-specific CTLs was observed in some HTLV-1-infected humanized mice.HTLV-1 Tax-specific CTLs were present at low frequency in blood and bone marrow, but at high frequency in lymphoid organs. The proviral load of mice in which Tax-specific CTLs were detected showed a suppressive trend in vivo, suggesting that the latent infection state of HTLV-1 is partially reproduced.
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| Free Research Field |
ウイルス学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究によりヒトと同様のHTLV-1感染状態を再現するHTLV-1感染ヒト化マウスモデルが確立されれば、ヒトではこれまで困難であった、生体内でのHTLV-1感染細胞と宿主免疫応答との相互作用の詳細な解析が可能となり、ATL病態発症過程における感染細胞のゲノム・エピゲノム的変化、ATL前駆細胞出現の時期・部位の同定等、ATL治療戦略における重要な知見が得られるものと期待される。また本モデルは、ワクチンを中心とした免疫学的治療法の開発・評価にも有用であり、HTLV-1のみならず様々なウイルス感染症の個体レベルでの実験的検証に寄与するものと期待される。
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