| 研究課題/領域番号 |
22K16375
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| 研究種目 |
若手研究
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| 配分区分 | 基金 |
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| 審査区分 |
小区分54030:感染症内科学関連
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| 研究機関 | 熊本大学 |
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研究代表者 |
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| 研究期間 (年度) |
2022-04-01 – 2025-03-31
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| 研究課題ステータス |
交付 (2023年度)
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| 配分額 *注記 |
4,680千円 (直接経費: 3,600千円、間接経費: 1,080千円)
2024年度: 1,170千円 (直接経費: 900千円、間接経費: 270千円)
2023年度: 1,690千円 (直接経費: 1,300千円、間接経費: 390千円)
2022年度: 1,820千円 (直接経費: 1,400千円、間接経費: 420千円)
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| キーワード | HIV-1 restriction |
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| 研究開始時の研究の概要 |
Proposed plan is outlined to be conducted within tow years. First plan is conducted in one year, and Plane B is conducted in the second year. Plane C will be conducted alongside other plans.
By third year, it is excepected to conclude all results and prepare paper for publication.
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| 研究実績の概要 |
Results showed iPS-ML derived macrophages are useful as a good model for investigating host/HIV-1 interaction in myeloid cells. Analysis of APOBEC3 family protein in iPS-ML cell showed differential expression of individual proteins (for example: A3A, A3G, A3F), and more importantly some cell lines express stable haplotypes of A3H. Furthermore, A3 proteins (specially A3G A3F) induced HIV-1 restriction in iPS-ML derived macrophages. This restriction is counteracted by the HIV-1 viral factor Vif.
As A3 poteins mediate HIV-1 restriction via inducing lethal mutations to HIV-1 genome, G- to -A mutations are signifcantly detected in the Vif-deficient HIV-1-infected iPS-ML cells. However, deaminase-independent mechanisms (no viral mutations) to restrict HIV-1 in iPS-ML cells are also suggested.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
Currently, one more staff joined this research project, which provided better handling of the planned investigations.
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| 今後の研究の推進方策 |
Future work will focus on determining the possible mechanisms to induce HIV-1 restriction in iPS-MLderived macrophages.
- analysis for A3-mediated viral mutations to identify frequency, magnitude and preferred sequences of A3 proteins to induce such restriction.
- analysis for HIV-1 reverse transcription (RT) and late RT products in order to clarify deaminase independent restriction.
- Creating modified iPS-ML derived macrophages (A3G deleted, A3F deleted, or A3A-A3G deleted cells), which will characterize the potential role of each individual protein to mediate HIV-1 restriction, as well as testing the potential to utilze A3-mediated mutagenesis to attain HIV-1 functional cure.
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