| Project/Area Number |
18K16122
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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 54010:Hematology and medical oncology-related
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| Research Institution | Saga University (2019)
Kumamoto University (2018) |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 成人T細胞白血病・リンパ腫 / HTLV-1 / キメラトランスクリプト / 次世代シークエンス解析 / 次世代シークエンシング / 成人T細胞白血病-リンパ腫 |
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| Outline of Final Research Achievements |
We hypothesized that the integrated provirus generates virus-host chimeric transcripts (CT) may play a role in the clonal selection of the HTLV-1-infected cell. HTLV-1 RNA-capture-seq provided the presence of CTs in 21 out of 30 ATL patients. We next quantified the abundance of CTs by droplet digital PCR, and found that the levels of CTs were similar to those of viral RNAs containing splice junction of HBZ, although the expression levels varied among different ATL cases. Oxford Nanopore sequencing revealed that the HTLV-1 provirus generates various splicing CTs with the host genes in both viral sense and antisense orientations. To clarify the impact of viral integration on clonal expansion, we analyzed HTLV-1-infected Jurkat cells. The integration site analysis showed that some clones were remarkably expanded during the long-term cultivation and some of them harbored CTs with the host genes.
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| Academic Significance and Societal Importance of the Research Achievements |
HTLV-1感染者のうち約5%のみで予後不良である成人T細胞白血病・リンパ腫(ATL)を発症する。わずか5%の感染者の体内で、どのようにATLクローンが選択されるかは、いまだに不明である。我々は組み込み部位特異的なキメラトランスクリプトが、多くのATLクローンで存在していることを確認した。またHTLV-1感染させたJurkat細胞株を用いたin vitroの研究でもキメラトランスクリプトの存在が確認され、感染クローン毎に増殖速度が異なっていることが確認された。ウイルスとホストのキメラトランスクリプトが新たなATLの発症機序の一つである可能性を示唆した。
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