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首页> 外文会议>International Conference on Biomedical Engineering in Vietnam >G-Quadruplexes in the Human Immunodeficiency Virus-1 and Herpes Simplex Virus-1: New Targets for Antiviral Activity by Small Molecules
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G-Quadruplexes in the Human Immunodeficiency Virus-1 and Herpes Simplex Virus-1: New Targets for Antiviral Activity by Small Molecules

机译：人类免疫缺陷病毒-1中的G-Quadruplees和单纯疱疹病毒-1：小分子的抗病毒活动的新靶标

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G-quadruplexes (G-4s) are G-rich non-canonical four-stranded conformations of nucleic acids that act as structural switches of cellular processes. Very little is known on the role of G-4s in viruses yet. The human immunodeficiency virus-1 (HIV-1) and the human herpes simplex virus-1 (HSV-1) are important human pathogens: HIV-1 is the etiological agent for the acquired immune deficiency syndrome (AIDS), while HSV-1 causes vesicular lesions on the mucous membranes, but it can also cause serious diseases, such as encephalitis, in immunocompromised patients and it increases sexual transmission of HIV-1. Both viruses permanently install into the human host and no cure to eradicate them has yet been developed. We have shown that DNA G-4s arise in the integrated DNA genome, in the long terminal repeat (LTR) promoter, and inhibit viral transcription. We now show that the LTR sequence is present also in the HIV-1 RNA genome where it can fold into very stable parallel-like G-4 structures. Both DNA and RNA G-4s were stabilized by a G-4 ligand, BRACO-19, which exerted antiviral activity against a broad range of virus strains, host cells and types of infections. BRACO-19 was active both at the reverse transcription step and during post-integration events, which are compatible with BRACO-19 activity on G-4 structures. Also HSV-1, which is characterized by a genome remarkably rich in guanines, presents clusters of repeated sequences forming very stable G-4s in key regions of the HSV-1 genome. Treatment of HSV-1 infected cells with BRACO-19 induced significant inhibition of virus production, general reduction of viral transcripts and of intracellular viral DNA. BRACO-19 was able to inhibit Taq polymerase processing at G-4 sites. This work, besides presenting the first evidence of extended G-4 sites in key regions of the HIV-1 and HSV-1 genomes, opens up new potential antiviral therapeutic interventions based on the use of G-4 ligands.
机译：G-四（G-4）是核酸富含G的非规范四股构象充当细胞过程的结构的开关。很少是在病毒的G-4S的作用尚未知。人类免疫缺陷病毒-1（HIV-1）和人单纯疱疹病毒1型（HSV-1）是重要的人类病原体：HIV-1是为获得性免疫缺陷综合征（AIDS）的病原体，而HSV-1导致对粘膜水泡，但它也可以引起严重的疾病，如脑炎，在免疫受损的患者和它增加HIV-1的性传播。这两种病毒永久安装到人类宿主和无药可治，消除他们还没有被开发出来。我们已经表明，DNA G-4S出现在整合的DNA的基因组，在长末端重复（LTR）启动子，和抑制病毒转录。我们现在表明，该LTR序列存在也是在HIV-1 RNA基因组，其中它可以折叠成非常稳定的平行状G-4的结构。 DNA和RNA两者G-4S通过一个G-4配体，布拉苏-19，其施加抗病毒活性针对广泛的病毒株，宿主细胞和感染类型的稳定化。布拉苏-19无论是在反转录步骤和在积分后的事件，这是与G-4结构布拉苏-19活性相容是活跃的。也HSV-1，它的特点是显着富含鸟嘌呤一个基因组中，重复序列的呈现簇形成在HSV-1基因组的关键区域非常稳定的G-4S。 HSV-1感染的细胞的治疗用布拉苏-19诱导病毒生产的显著抑制，病毒转录物和细胞内病毒DNA的一般减少。布拉苏-19能够抑制Taq聚合酶处理在G-4位点。这项工作，除了展示推广G-4点的第一个证据在HIV-1和HSV-1基因组的重点地区，开辟了基于使用G-4配体的新的潜在的抗病毒治疗干预。

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