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タイトル: | N4BP1 restricts HIV-1 and its inactivation by MALT1 promotes viral reactivation |
著者: | Yamasoba, Daichi Sato, Kei Ichinose, Takuya Imamura, Tomoko Koepke, Lennart Joas, Simone Reith, Elisabeth Hotter, Dominik Misawa, Naoko Akaki, Kotaro Uehata, Takuya Mino, Takashi https://orcid.org/0000-0002-9562-008X (unconfirmed) Miyamoto, Sho Noda, Takeshi https://orcid.org/0000-0002-0658-4663 (unconfirmed) Yamashita, Akio Standley, Daron M. Kirchhoff, Frank Sauter, Daniel Koyanagi, Yoshio https://orcid.org/0000-0002-3007-6642 (unconfirmed) Takeuchi, Osamu https://orcid.org/0000-0002-1260-6232 (unconfirmed) |
著者名の別形: | 山岨, 大智 佐藤, 佳 市野瀬, 拓也 今村, 智子 三沢, 尚子 赤木, 宏太朗 植畑, 拓也 三野, 享史 野田, 岳志 山下, 暁朗 小柳, 義夫 竹内, 理 |
キーワード: | HIV infections Restriction factors RNA decay |
発行日: | Sep-2019 |
出版者: | Springer Science and Business Media LLC |
誌名: | Nature Microbiology |
巻: | 4 |
号: | 9 |
開始ページ: | 1532 |
終了ページ: | 1544 |
抄録: | RNA-modulating factors not only regulate multiple steps of cellular RNA metabolism, but also emerge as key effectors of the immune response against invading viral pathogens including human immunodeficiency virus type-1 (HIV-1). However, the cellular RNA-binding proteins involved in the establishment and maintenance of latent HIV-1 reservoirs have not been extensively studied. Here, we screened a panel of 62 cellular RNA-binding proteins and identified NEDD4-binding protein 1 (N4BP1) as a potent interferon-inducible inhibitor of HIV-1 in primary T cells and macrophages. N4BP1 harbours a prototypical PilT N terminus-like RNase domain and inhibits HIV-1 replication by interacting with and degrading viral mRNA species. Following activation of CD4+ T cells, however, N4BP1 undergoes rapid cleavage at Arg 509 by the paracaspase named mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1). Mutational analyses and knockout studies revealed that MALT1-mediated inactivation of N4BP1 facilitates the reactivation of latent HIV-1 proviruses. Taken together, our findings demonstrate that the RNase N4BP1 is an efficient restriction factor of HIV-1 and suggest that inactivation of N4BP1 by induction of MALT1 activation might facilitate elimination of latent HIV-1 reservoirs. |
記述: | 宿主がHIV-1感染を抑制する新たなメカニズムの解明 --N4BP1によるRNA分解とその調節がウイルス再活性化を調節する--. 京都大学プレスリリース. 2019-05-29. |
著作権等: | This is the accepted manuscript of the article, which has been published in final form at https://doi.org/10.1038/s41564-019-0460-3. The full-text file will be made open to the public on 27 November 2019 in accordance with publisher's 'Terms and Conditions for Self-Archiving'. This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。 |
URI: | http://hdl.handle.net/2433/244207 |
DOI(出版社版): | 10.1038/s41564-019-0460-3 |
PubMed ID: | 31133753 |
関連リンク: | https://www.kyoto-u.ac.jp/ja/research-news/2019-05-29 |
出現コレクション: | 学術雑誌掲載論文等 |
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