Genomic RNA folding mediates assembly of human parechovirus.
Genomic RNA folding mediates assembly of human parechovirus.
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DOI：
10.1038/s41467-016-0011-z
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发表时间：
2017-02-23
影响因子：
16.6
通讯作者：
Twarock R
中科院分区：
文献类型：
--
作者：
Shakeel S;Dykeman EC;White SJ;Ora A;Cockburn JJB;Butcher SJ;Stockley PG;Twarock R
小航行虫科的主要病毒病原体的组装还知之甚少。人类副病毒1型就是这类病毒的一个例子，它包含60个RNA密度有序的短区，与蛋白质壳进行相同的接触。在这里，我们通过指数浓缩、生物信息学分析和反向遗传学基于RNA的系统进化的组合表明，这些RNA片段以序列特异性的方式与外壳蛋白结合。RNA外壳蛋白识别基序或其接触氨基酸残基的破坏对病毒组装是有害的。这些数据与在病毒粒子组装中发挥重要作用的RNA包装信号是一致的。它们在外壳蛋白上的结合位点在进化上在副病毒属中是保守的，表明它们是潜在的广谱抗病毒靶点。对于人类副冠状病毒，基因组RNA包装成病毒颗粒的潜在机制还不是很清楚。在这里，作者确定了副病毒基因组中与衣壳蛋白结合的短RNA基序，为病毒粒子组装提供了大约60个特定的相互作用。
Assembly of the major viral pathogens of the Picornaviridae family is poorly understood. Human parechovirus 1 is an example of such viruses that contains 60 short regions of ordered RNA density making identical contacts with the protein shell. We show here via a combination of RNA-based systematic evolution of ligands by exponential enrichment, bioinformatics analysis and reverse genetics that these RNA segments are bound to the coat proteins in a sequence-specific manner. Disruption of either the RNA coat protein recognition motif or its contact amino acid residues is deleterious for viral assembly. The data are consistent with RNA packaging signals playing essential roles in virion assembly. Their binding sites on the coat proteins are evolutionarily conserved across the Parechovirus genus, suggesting that they represent potential broad-spectrum anti-viral targets. The mechanism underlying packaging of genomic RNA into viral particles is not well understood for human parechoviruses. Here the authors identify short RNA motifs in the parechovirus genome that bind capsid proteins, providing approximately 60 specific interactions for virion assembly.