Establishment of breeding colony of tree shrews (Tupaia belangeri) for HBV chronic infected animal model and genome sequence analysis

• Project/Area Number: 17K08873
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: National Institutes of Biomedical Innovation, Health and Nutrition
• Principal Investigator: Takano Jun-ichiro 国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 霊長類医科学研究センター, 研究員 (20416275)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: B型肝炎ウイルス / 感染動物モデル / ツパイ / ウイルス / 感染症 / 動物モデル / 遺伝子変異

Outline of Final Research Achievements

In this study, to establish a chronic HBV infection animal model, HBV molecular clone was constructed for obtaining highly sensitive tree shrew (Tupaia belangeri) lines and evaluating HBV genomic mutation in tree shrews which have functional immune systems. However low-level HBV viral loads were confirmed and we could not evaluate DNA sequence variation, detection rates indicated that helpfulness of HBV molecular clone in tree shrews. The comparison detection rate between F1 and F2 showed F2 tree shews were highly sensitive for HBV. Furthermore, hepatocellular carcinoma was confirmed in a F1 tree shrew. Our study showed the possibility of establishment of chronic HBV infection tree shrew model and its usefulness for future studies.

Academic Significance and Societal Importance of the Research Achievements

本研究でのツパイを用いたHBV感染実験では、まだ規模が小さいながら、300週齢の個体で肝臓の腫瘍化が確認できた。また、血中ウイルス量は低いものの検出率での比較ではF2群ではF1群の2倍の検出率であり、世代を重ねることによって感受性を高められる可能性も示唆された。ヒトとチンパンジー以外で唯一自然免疫状態で感受性のあるツパイの感染モデルの可能性が確認でき、治療効果の判定などでヒトへのトランスレーショナルリサーチが期待できる。