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2023 Fiscal Year Final Research Report

• Project/Area Number: 19K08357
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Nojima Kiyoko 国立感染症研究所, 次世代生物学的製剤研究センター, 主任研究官 (60370970)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: HTLV-1 / 母子感染 / クローン解析

Outline of Final Research Achievements

Mother-to-child transmission of HTLV-1 occurs in 3-5% of cases even when switching to exclusive formula feeding, suggesting the possibility of transplacental or intrapartum transmission. There was a need for animal models to help elucidate the mechanism of mother-to-child transmission. In this study, we developed a mother-to-child infection model by HTLV-1 infected pregnant humanized mice, created by transplanting human peripheral blood into NOG mice. Clonal analysis of genomes derived from the placenta of pregnant mother mice and fetal liver revealed the presence of small number of common clones across all tissues. Small numbers of common clones were also in the blood and breast milk of infected nursing mother mice, as well as in the liver genomes of newborn mice, suggesting the possibility of de novo infection. This study mimics HTLV-1 mother-to-child transmission and is suggested to be useful for future therapeutic drug development.

Free Research Field

ウイルス学、品質管理

Academic Significance and Societal Importance of the Research Achievements

ヒトT細胞白血病ウイルス (HTLV-1) は完全人工栄養乳に切り替えても、3-5%程度の母子感染が認められることから，経胎盤感染あるいは経産道感染の可能性が示唆されてきたが，感染機序の解明にはHTLV-1キャリアの出産後の胎盤や臍帯などの調査だけでは難しく，母子感染動物モデルの開発が望まれていた。我々は、妊娠初期のNOGマウスにヒト末梢血を移植しヒト化することで妊娠ヒト化マウスを作成後，HTLV-1感染細胞を移植することにより、母子感染モデルを構築し実験に用いた。本感染モデルは、胎生期におけるHTLV-1感染細胞の動態および感染機構の解明や治療薬開発等に役立てられると考えられる。