Chemical Targeting of a G-Quadruplex RNA in the Ebola Virus L Gene
Chemical Targeting of a G-Quadruplex RNA in the Ebola Virus L Gene
复制标题
埃博拉病毒 L 基因中 G-四链体 RNA 的化学靶向。
DOI：
10.1016/j.chembiol.2016.07.019
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发表时间：
2016-09-22
影响因子：
8.6
通讯作者：
Zhou, Xiang
中科院分区：
文献类型：
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作者：
Wang, Shao-Ru;Zhang, Qiu-Yan;Zhou, Xiang
在本研究中，我们的生物信息学分析首次揭示了扎伊尔埃博拉病毒L基因中存在一个保守的富含鸟嘌呤的序列。使用各种方法，我们表明该序列倾向于折叠成g -四重RNA。TMPyP4处理在RNA水平上明显抑制L基因表达。此外，迷你复制子实验表明，TMPyP4有效抑制人工扎伊尔埃博拉病毒迷你基因组，是一种比利巴韦林更有效的抑制剂。虽然TMPyP4处理减少了突变体迷你基因组的复制，但当L基因中g -四重体形成被消除时，其抑制作用与野生型相比显著减轻。因此，我们的发现提供了g -四重体RNA存在于负义RNA病毒中的第一个证据。最后，g -四重体RNA稳定可能是对抗埃博拉病毒病的一种新的治疗策略。
In the present study, our bioinformatics analysis first reveals the existence of a conserved guanine-rich sequence within the Zaire ebolavirus L gene. Using various methods, we show that this sequence tends to fold into G-quadruplex RNA. TMPyP4 treatment evidently inhibits L gene expression at the RNA level. Moreover, the mini-replicon assay demonstrates that TMPyP4 effectively inhibits the artificial Zaire ebolavirus mini-genome and is a more potent inhibitor than ribavirin. Although TMPyP4 treatment reduced the replication of the mutant mini-genome when G-quadruplex formation was abolished in the L gene, its inhibitory effect was significantly alleviated compared with wild-type. Our findings thus provide the first evidence that G-quadruplex RNA is present in a negative-sense RNA virus. Finally, G-quadruplex RNA stabilization may represent a new therapeutic strategy against Ebola virus disease.