期刊
ACS INFECTIOUS DISEASES
卷 5, 期 12, 页码 2127-2135出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsinfecdis.9b00272
关键词
G-quadruplexes; HIV-1 nucleocapsid protein; NCp7; reverse transcription; BRACO-19
资金
- European Research Council (ERC) [615879]
- Bill and Melinda Gates Foundation [OPP1035881, OPP1097238]
- Bill and Melinda Gates Foundation [OPP1035881, OPP1097238] Funding Source: Bill and Melinda Gates Foundation
The G-quadruplexes that form in the HIV-1 RNA genome hinder progression of reverse transcriptase in vitro, but not in infected cells. We investigated the possibility that the HIV-1 nucleocapsid protein NCp7, which remains associated with the viral RNA during reverse transcription, modulated HIV-1 RNA G-quadruplex stability. By electrophoresis, circular dichroism, mass spectrometry, and reverse transcriptase stop assays, we demonstrated that NCp7 binds and unfolds the HIV-1 RNA G-quadruplexes and promotes DNA/RNA duplex formation, allowing reverse transcription to proceed. The G-quadruplex ligand BRACO-19 was able to partially counteract this effect. These results indicate NCp7 as the first known viral protein able to unfold RNA G-quadruplexes, and they explain how the extra-stable HIV-1 RNA G-quadruplexes are processed; they also point out that the reverse transcription process is hindered by G-quadruplex ligands at both reverse transcriptase and NCp7 level. This information can lead to the development of more effective anti-HIV-1 drugs with a new mechanism of action.
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