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The identification of a small molecule compound that reduces HIV-1 nef-mediated viral infectivity enhancement
http://hdl.handle.net/2298/24401
http://hdl.handle.net/2298/244018551fc8e-b5d5-41b5-9e3b-2d72492745b2
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
journal.pone.0027696.pdf (1.5 MB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2012-05-07 | |||||
| タイトル | ||||||
| タイトル | The identification of a small molecule compound that reduces HIV-1 nef-mediated viral infectivity enhancement | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 主題 | AIDS, HIV-1 | |||||
| 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 |
Chutiwitoonchai, Nopporn
× Chutiwitoonchai, Nopporn× Hiyoshi, Masateru× Mwimanzi, Philip× Ueno, Takamasa× Adachi, Akio× Ode, Hirotaka× Sato, Hironori× Fackler, Oliver T.× 岡田, 誠治× Suzu, Shinya |
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| 別言語の著者 |
上野, 貴將
× 上野, 貴將× 岡田, 誠治× 鈴, 伸也 |
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| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Nef is a multifunctional HIV-1 protein that accelerates progression to AIDS, and enhances the infectivity of progeny viruses through a mechanism that is not yet understood. Here, we show that the small molecule compound 2c reduces Nef-mediated viral infectivity enhancement. When added to viral producer cells, 2c did not affect the efficiency of viral production itself. However, the infectivity of the viruses produced in the presence of 2c was significantly lower than that of control viruses. Importantly, an inhibitory effect was observed with Nef+ wild-type viruses, but not with viruses produced in the absence of Nef or in the presence of proline-rich PxxP motif-disrupted Nef, both of which displayed significantly reduced intrinsic infectivity. Meanwhile, the overexpression of the SH3 domain of the tyrosine kinase Hck, which binds to a PxxP motif in Nef, also reduced viral infectivity. Importantly, 2c inhibited Hck SH3-Nef binding, which was more marked when Nef was pre-incubated with 2c prior to its incubation with Hck, indicating that both Hck SH3 and 2c directly bind to Nef and that their binding sites overlap. These results imply that both 2c and the Hck SH3 domain inhibit the interaction of Nef with an unidentified host protein and thereby reduce Nef-mediated infectivity enhancement. The first inhibitory compound 2c is therefore a valuable chemical probe for revealing the underlying molecular mechanism by which Nef enhances the infectivity of HIV-1. | |||||
| 書誌情報 |
PLoS ONE 巻 6, 号 11, p. 1-12, 発行年 2011-11 |
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| ISSN | ||||||
| 収録物識別子 | 1932-6203 | |||||
| DOI | ||||||
| 関連タイプ | isIdenticalTo | |||||
| 関連識別子 | 10.1371/journal.pone.0027696 | |||||
| 権利 | ||||||
| 権利情報 | © 2011 Public Library of Science | |||||
| フォーマット | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | application/pdf | |||||
| フォーマット | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | application/pdf | |||||
| 形態 | ||||||
| 値 | 1455355 bytes | |||||
| 形態 | ||||||
| 値 | 58459 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 | 490 | |||||
| 出版者 | ||||||
| 出版者 | Public Library of Science | |||||
| 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 | http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0027696 | |||||
| コメント | ||||||
| 値 | Article number e27696 | |||||
