Structural analysis of 3'UTRs in insect flaviviruses reveals novel determinant of sfRNA biogenesis and provides new insights into flavivirus evolution
Structural analysis of 3'UTRs in insect flaviviruses reveals novel determinant of sfRNA biogenesis and provides new insights into flavivirus evolution
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昆虫黄病毒 3UTR 的结构分析揭示了 sfRNA 生物发生的新决定因素，并为黄病毒进化提供了新见解
DOI：
10.1101/2021.06.23.449515
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Slonchak A
中科院分区：
文献类型：
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作者：
Slonchak A
亚基因组黄病毒RNA（sfRNA）是由致病性蚊媒黄病毒（MBF）产生的病毒源性非编码RNA，用于对抗宿主的抗病毒反应。迄今为止，非致病性黄病毒产生和利用sfRNA的能力在很大程度上仍未被探索，并且不清楚XRN1抗性在黄病毒进化和宿主适应中起什么作用。本文显示了由仅在蚊子中复制的几种昆虫特异性黄病毒（ISF）产生的sfRNA，并确定了其完整3'UTR的二级结构。还鉴定了负责ISF sfRNA生物发生的xrRNA，并证明了这些sfRNA在病毒复制中的作用。我们证明了所有经典ISF的3'UTR，除了按蚊属相关病毒，以及双宿主相关ISF Binjari病毒都含有重复的xrRNA。我们还揭示了新的结构元件在3'UTR的双重主机相关和Anoproteins相关的经典ISFs。基于结构的系统发育分析表明，在按蚊种相关ISF中鉴定的xrRNA可能是ISF和MBF xrRNA的祖先。此外，我们的数据提供了证据，证明在黄病毒的进化中选择了重复的xrRNA以提供功能冗余，如果其中一种结构因突变或错误折叠而失效，则保留了sfRNA的产生。
Subgenomic flaviviral RNAs (sfRNAs) are virus-derived noncoding RNAs produced by pathogenic mosquito-borne flaviviruses (MBF) to counteract the host antiviral response. To date, the ability of non-pathogenic flaviviruses to produce and utilise sfRNAs remains largely unexplored, and it is unclear what role XRN1 resistance plays in flavivirus evolution and host adaptation. Herein the production of sfRNAs by several insect-specific flaviviruses (ISFs) that replicate exclusively in mosquitoes is shown, and the secondary structures of their complete 3’UTRs are determined. The xrRNAs responsible for the biogenesis of ISF sfRNAs are also identified, and the role of these sfRNAs in virus replication is demonstrated. We demonstrate that 3’UTRs of all classical ISFs, exceptAnopheles spp-asscoaited viruses, and of the dual-host associated ISF Binjari virus contain duplicated xrRNAs. We also reveal novel structural elements in the 3’UTRs of dual host-associated andAnopheles-associated classical ISFs. Structure-based phylogenetic analysis demonstrates that xrRNAs identified inAnopheles spp-associated ISF are likely ancestral to xrRNAs of ISFs and MBFs. In addition, our data provide evidence that duplicated xrRNAs are selected in the evolution of flaviviruses to provide functional redundancy, which preserves the production of sfRNAs if one of the structures is disabled by mutations or misfolding.