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Sporadic on/off switching of HTLV-1 Tax expression is crucial to maintain the whole population of virus-induced leukemic cells
http://hdl.handle.net/2298/41361
http://hdl.handle.net/2298/41361fff3e4df-617c-431e-b77b-ceeccfa7b631
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
Mahgoub_PNAS_2018.pdf (1.6 MB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2019-01-15 | |||||
| タイトル | ||||||
| タイトル | Sporadic on/off switching of HTLV-1 Tax expression is crucial to maintain the whole population of virus-induced leukemic cells | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 主題 | HTLV-1, Tax, HBZ, adult T-cell leukemia–lymphoma | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| 著者 |
Mohamed, Mahgoub
× Mohamed, Mahgoub× Yasunaga, Jun-ichirou× Iwami, Shingo× Nakaoka, Shinji× Koizumi, Yoshiki× Shimura, Kazuya× Matsuoka, Masao |
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| 別言語の著者 |
松岡, 雅雄
× 松岡, 雅雄 |
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| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Viruses causing chronic infection artfully manipulate infected cells to enable viral persistence in vivo under the pressure of immunity. Human T-cell leukemia virus type 1 (HTLV-1) establishes persistent infection mainly in CD4+ T cells in vivo and induces leukemia in this subset. HTLV-1–encoded Tax is a critical transactivator of viral replication and a potent oncoprotein, but its significance in pathogenesis remains obscure due to its very low level of expression in vivo. Here, we show that Tax is expressed in a minor fraction of leukemic cells at any given time, and importantly, its expression spontaneously switches between on and off states. Live cell imaging revealed that the average duration of one episode of Tax expression is ∼19 hours. Knockdown of Tax rapidly induced apoptosis in most cells, indicating that Tax is critical for maintaining the population, even if its short-term expression is limited to a small subpopulation. Single-cell analysis and computational simulation suggest that transient Tax expression triggers antiapoptotic machinery, and this effect continues even after Tax expression is diminished; this activation of the antiapoptotic machinery is the critical event for maintaining the population. In addition, Tax is induced by various cytotoxic stresses and also promotes HTLV-1 replication. Thus, it seems that Tax protects infected cells from apoptosis and increases the chance of viral transmission at a critical moment. Keeping the expression of Tax minimal but inducible on demand is, therefore, a fundamental strategy of HTLV-1 to promote persistent infection and leukemogenesis. | |||||
| 書誌情報 |
PNAS 巻 115, 号 6, p. E1269-E1278, 発行年 2018-01-22 |
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| ISSN | ||||||
| 収録物識別子 | 00278424 | |||||
| DOI | ||||||
| 関連タイプ | isIdenticalTo | |||||
| 関連識別子 | https://doi.org/10.1073/pnas.1715724115 | |||||
| フォーマット | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | application/pdf | |||||
| 形態 | ||||||
| 値 | 1599085 bytes | |||||
| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
| 日本十進分類法 | ||||||
| 主題Scheme | NDC | |||||
| 主題 | 491 | |||||
| 出版者 | ||||||
| 出版者 | National Academy of Sciences | |||||
| 資源タイプ | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 論文(Article) | |||||
| 資源タイプ・ローカル | ||||||
| 値 | 雑誌掲載論文 | |||||
| 資源タイプ・NII | ||||||
| 値 | Journal Article | |||||
| 資源タイプ・DCMI | ||||||
| 値 | text | |||||
| 資源タイプ・ローカル表示コード | ||||||
| 値 | 01 | |||||
| URL | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | https://www.pnas.org/content/115/6/E1269 | |||||
