| Item type |
文献 / Documents(1) |
| 公開日 |
2024-10-11 |
| アクセス権 |
|
|
アクセス権 |
open access |
|
アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 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 |
| item_1722929371688 |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.1371/journal.pone.0027696 |
|
|
言語 |
ja |
|
|
関連名称 |
10.1371/journal.pone.0027696 |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| 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 |
en |
| タイトル別表記 |
|
|
その他のタイトル |
Small Molecule Inhibition of HIV-1 Infectivity |
|
言語 |
en |
| 著者 |
Chutiwitoonchai, Nopporn
Hiyoshi, Masateru
Mwimanzi, Philip
Ueno, Takamasa
足立, 昭夫
Ode, Hirotaka
Sato, Hironori
Fackler, Oliver T.
Okada, Seiji
Suzu, Shinya
|
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
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. |
|
言語 |
en |
| bibliographic_information |
en : PLOS ONE
巻 6,
号 11,
p. e27696,
発行日 2011-11-15
|
| 収録物ID |
|
|
収録物識別子タイプ |
EISSN |
|
収録物識別子 |
19326203 |
| 出版者 |
|
|
出版者 |
PLOS |
|
言語 |
en |
| item_10001_rights_15 |
|
|
言語 |
en |
|
権利情報 |
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| item_1723180141928 |
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|
識別子 |
250402 |
|
識別子タイプ |
URI |
| 言語 |
|
|
言語 |
eng |
pone_6_11_e27696.pdf (1.4 MB)
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