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A New Subclass of Exoribonuclease-Resistant RNA Found in Multiple Genera of Flaviviridae
mBio ( IF 6.4 ) Pub Date : 2020-09-29 , DOI: 10.1128/mbio.02352-20
Matthew J Szucs 1 , Parker J Nichols 1 , Rachel A Jones 1 , Quentin Vicens 2 , Jeffrey S Kieft 2, 3
Affiliation  

Viruses have developed innovative strategies to exploit the cellular machinery and overcome the antiviral defenses of the host, often using specifically structured RNA elements. Examples are found in the Flavivirus genus (in the family Flaviviridae), where during flaviviral infection, pathogenic subgenomic flaviviral RNAs (sfRNAs) accumulate in the cell. These sfRNAs are formed when a host cell 5′ to 3′ exoribonuclease degrades the viral genomic RNA but is blocked by an exoribonuclease-resistant RNA structure (xrRNA) located in the viral genome’s 3′ untranslated region (UTR). Although known to exist in several Flaviviridae genera, the full distribution and diversity of xrRNAs in this family were unknown. Using the recently solved high-resolution structure of an xrRNA from the divergent flavivirus Tamana bat virus (TABV) as a reference, we used bioinformatic searches to identify xrRNAs in the remaining three genera of Flaviviridae: Pegivirus, Pestivirus, and Hepacivirus. We biochemically and structurally characterized several examples, determining that they are genuine xrRNAs with a conserved fold. These new xrRNAs look superficially similar to the previously described xrRNAs but possess structural differences making them distinct from previous classes of xrRNAs. Overall, we have identified the presence of xrRNA in all four genera of Flaviviridae, but not in all species. Our findings thus require adjustments of previous xrRNA classification schemes and expand the previously known distribution of xrRNA in Flaviviridae.

中文翻译:

在黄病毒科的多个属中发现的一种新的耐外切核酸酶的亚类

病毒已经开发出创新的策略来利用细胞机制并克服宿主的抗病毒防御,通常使用特定结构的RNA元件。在黄病毒属(黄病毒科)中发现了例子,在黄病毒感染期间,病原性亚基因组黄病毒RNA(sfRNA)积累在细胞中。当宿主细胞5'至3'核糖核酸外切酶降解病毒基因组RNA但被位于病毒基因组3'非翻译区(UTR)中的核糖核酸外切酶抗性RNA结构(xrRNA)阻断时,形成这些sfRNA。虽然已知存在于几种黄病毒科中属,该家族中xrRNA的完整分布和多样性尚不清楚。以最近解散的黄病毒塔马纳蝙蝠病毒(TABV)的xrRNA的高分辨率结构为参考,我们使用生物信息学搜索来鉴定黄病毒科的其余三个属中的xrRNAPegivirusPestivirusHepacivirus。我们对几个示例进行了生物化学和结构表征,确定它们是具有保守折叠的真正xrRNA。这些新的xrRNA表面上看起来类似于先前描述的xrRNA,但具有结构差异,使其与以前的xrRNA类型不同。总的来说,我们已经鉴定出xrRNA在所有四个属中都存在。黄病毒科,但不是所有物种。因此,我们的发现需要调整以前的xrRNA分类方案,并扩大黄病毒科中xrRNA的已知分布
更新日期:2020-10-28
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