The structure of the influenza A virus genome
The structure of the influenza A virus genome
复制标题
甲型流感病毒基因组的结构
DOI：
10.1101/236620
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Dadonaite B
中科院分区：
文献类型：
--
作者：
Dadonaite B
甲型流感病毒（IAV）对人类健康构成重大威胁。IAV基因组由八个单链病毒RNA片段组成，这些片段包含在单独的病毒核糖核蛋白（vRNP）复合物中，这些复合物一起包装成单个病毒颗粒。病毒RNA的结构被认为在将不同的vRNP组装成出芽的病毒体中起作用，并且在引导IAV之间的重配中起作用。已确定的人类IAV与动物宿主中携带的IAV之间的重配可导致出现大流行性流感毒株，而在人群中几乎没有预先存在的免疫力。虽然以前的研究已经揭示了vRNP内蛋白质的整体组织，但使用常规结构方法表征病毒RNA结构受到有限分辨率和无法解析动态组分的阻碍。在这里，我们采用多种高通量测序方法来生成IAV基因组的全局高分辨率结构。我们发现，不同的IAV基因组片段获得不同的RNA构象，并形成流感病毒粒子内的内部和片段间的RNA相互作用。我们使用我们详细的IAV基因组结构图，为不同IAV毒株之间的重配过程中片段间RNA相互作用如何驱动vRNP共分离提供直接证据。这里介绍的工作是一个路线图，既为开发改进的疫苗株，并为创建一个框架，以“风险评估”的重组潜力，以更好地预测新的大流行性流感病毒株的出现。
Influenza A viruses (IAVs) constitute a major threat to human health. The IAV genome consists of eight single-stranded viral RNA segments contained in separate viral ribonucleoprotein (vRNP) complexes that are packaged together into a single virus particle. The structure of viral RNA is believed to play a role in assembling the different vRNPs into budding virions, , , , , , –and in directing reassortment between IAVs. Reassortment between established human IAVs and IAVs harboured in the animal reservoir can lead to the emergence of pandemic influenza strains to which there is little pre-existing immunity in the human population,. While previous studies have revealed the overall organization of the proteins within vRNPs, characterization of viral RNA structure using conventional structural methods is hampered by limited resolution and an inability to resolve dynamic components,. Here, we employ multiple high-throughput sequencing approaches to generate a global high-resolution structure of the IAV genome. We show that different IAV genome segments acquire distinct RNA conformations and form both intra- and intersegment RNA interactions inside influenza virions. We use our detailed map of IAV genome structure to provide direct evidence for how intersegment RNA interactions drive vRNP cosegregation during reassortment between different IAV strains. The work presented here is a roadmap both for the development of improved vaccine strains and for the creation of a framework to ‘risk assess’ reassortment potential to better predict the emergence of new pandemic influenza strains.
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DOI：
10.1038/nrmicro.2016.87
发表时间：
2016-08
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Te Velthuis AJ;Fodor E
通讯作者：
Fodor E
影响因子：
16.6
作者：
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通讯作者：
Juozapaitis, Mindaugas
DOI：
10.1261/rna.042374.113
发表时间：
2013-12
期刊：
RNA (New York, N.Y.)
影响因子：
--
作者：
Turner R;Shefer K;Ares M Jr
通讯作者：
Ares M Jr
影响因子：
14.9
作者：
Lee N;Le Sage V;Nanni AV;Snyder DJ;Cooper VS;Lakdawala SS
通讯作者：
Lakdawala SS
影响因子：
1.2
作者：
Aw, Jong Ghut Ashley;Shen, Yang;Wan, Yue
通讯作者：
Wan, Yue