NMR structure of Dengue West Nile viruses stem-loop B: A key cis-acting element for flavivirus replication.
NMR structure of Dengue West Nile viruses stem-loop B: A key cis-acting element for flavivirus replication.
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DOI：
10.1016/j.bbrc.2020.07.115
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发表时间：
2020-08
影响因子：
3.1
通讯作者：
Shrikant Sharma;G. Varani
中科院分区：
文献类型：
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作者：
Shrikant Sharma;G. Varani
黄病毒是一种主要的新兴人类致病病毒，对全球健康构成持续和日益严重的威胁。它们是具有正极性的有包膜单链RNA病毒，由节肢动物载体如蚊子或蜱传播，导致大量和越来越多的人类死亡和疾病。5′-和3′-非翻译区（UTR）是高度结构化的，包含参与病毒翻译、复制和宿主适应的保守的顺式作用RNA元件。尽管它们在黄病毒复制中起作用，但很少有高分辨率结构研究调查病毒复制所需的RNA元件。在这里，我们报告的茎环B从WNV和DENV 4病毒的NMR结构。由于该元件是基因组环化和复制性病毒酶活性所必需的，因此病毒复制速率对这些RNA中即使很小的变化也很敏感。因此，这项工作提供了一个新的药物靶点，以减少黄病毒复制率的结构洞察。
Flaviviruses are major emerging human pathogenic viruses that pose a persistent and growing menace to global health. They are enveloped single-stranded RNA viruses with positive polarity transmitted by arthropod vectors like mosquitoes or ticks, responsible for a significant and growing number of human deaths and illnesses. The 5′- and 3′-untranslated regions (UTRs) are highly structured and contain conserved cis-acting RNA elements that participate in viral translation, replication and host adaptation. Despite their role in fiaviviruses replication, few high-resolution structural studies have investigated the RNA elements required for viral replication. Here we report the NMR structures of stem-loop B from WNV and DENV4 viruses. Because this element is required for cyclization of the genome and the activity of the replicative viral enzymes, viral replication rates are sensitive to even small changes in these RNAs. Therefore, this work provides structural insight into a new drug target to reduce flavivirus replication rates.