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HIV-1 Nucleocapsid Protein Unfolds Stable RNA G-Quadruplexes in the Viral Genome and Is Inhibited by G-Quadruplex Ligands.
ACS Infectious Diseases ( IF 4.0 ) Pub Date : 2019-11-06 , DOI: 10.1021/acsinfecdis.9b00272 Elena Butovskaya 1 , Paola Soldà 1 , Matteo Scalabrin 1 , Matteo Nadai 1 , Sara N Richter 1
ACS Infectious Diseases ( IF 4.0 ) Pub Date : 2019-11-06 , DOI: 10.1021/acsinfecdis.9b00272 Elena Butovskaya 1 , Paola Soldà 1 , Matteo Scalabrin 1 , Matteo Nadai 1 , Sara N Richter 1
Affiliation
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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.
中文翻译：
HIV-1核衣壳蛋白在病毒基因组中展开稳定的RNA G-Quadruplexes，并被G-Quadruplex配体抑制。
HIV-1 RNA基因组中形成的G四联体在体外可阻止逆转录酶的进程，但在受感染的细胞中则不会。我们调查了在逆转录过程中仍与病毒RNA结合的HIV-1核衣壳蛋白NCp7调节HIV-1 RNA G-四链体稳定性的可能性。通过电泳，圆二色性，质谱和逆转录酶终止试验，我们证明NCp7结合并展开HIV-1 RNA G四联体并促进DNA / RNA双链体形成，从而允许进行逆转录。G-四链体配体BRACO-19能够部分抵消这种作用。这些结果表明NCp7是第一个已知的能够展开RNA G四联体的病毒蛋白，它们解释了如何处理超稳定的HIV-1 RNA G四联体。他们还指出，逆转录酶和NCp7水平的G-四链体配体均阻碍了逆转录过程。这些信息可以导致开发具有新作用机制的更有效的抗HIV-1药物。
更新日期：2019-11-06
中文翻译：
HIV-1核衣壳蛋白在病毒基因组中展开稳定的RNA G-Quadruplexes，并被G-Quadruplex配体抑制。
HIV-1 RNA基因组中形成的G四联体在体外可阻止逆转录酶的进程，但在受感染的细胞中则不会。我们调查了在逆转录过程中仍与病毒RNA结合的HIV-1核衣壳蛋白NCp7调节HIV-1 RNA G-四链体稳定性的可能性。通过电泳，圆二色性，质谱和逆转录酶终止试验，我们证明NCp7结合并展开HIV-1 RNA G四联体并促进DNA / RNA双链体形成，从而允许进行逆转录。G-四链体配体BRACO-19能够部分抵消这种作用。这些结果表明NCp7是第一个已知的能够展开RNA G四联体的病毒蛋白，它们解释了如何处理超稳定的HIV-1 RNA G四联体。他们还指出，逆转录酶和NCp7水平的G-四链体配体均阻碍了逆转录过程。这些信息可以导致开发具有新作用机制的更有效的抗HIV-1药物。
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