A Highly Structured, Nuclease-Resistant, Noncoding RNA Produced by Flaviviruses Is Required for Pathogenicity
A Highly Structured, Nuclease-Resistant, Noncoding RNA Produced by Flaviviruses Is Required for Pathogenicity
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DOI：
10.1016/j.chom.2008.10.007
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发表时间：
2008-12-11
影响因子：
30.3
通讯作者：
Khromykh, Alexander A.
中科院分区：
文献类型：
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作者：
Pijlman, Gorben P.;Funk, Anneke;Khromykh, Alexander A.
病毒非编码RNA在病毒-宿主相互作用中发挥重要作用，促进病毒复制。我们报告说，黄病毒属的成员，一个医学上重要的脑炎RNA病毒的大组，产生一个独特的和高度结构化的非编码RNA的0.3-0.5 kb来自3'非翻译区的病毒基因组。使用西尼罗河病毒作为模型，我们表明，这种亚基因组RNA是由细胞核糖核酸酶的病毒基因组RNA的不完全降解的产物。位于3'非翻译区起始处的高度保守的RNA结构使该RNA对核酸酶具有抗性，并且所得的亚基因组RNA产物对于病毒诱导的细胞病变性和致病性是必需的。因此，黄病毒进化出一种独特的策略来产生一种非编码RNA产物，使它们能够更有效地杀死宿主。
Viral noncoding RNAs have been shown to play an important role in virus-host interplay to facilitate virus replication. We report that members of the genus Flavivirus, a large group of medically important encephalitic RNA viruses, produce a unique and highly structured noncoding RNA of 0.3-0.5 kb derived from the 3' untranslated region of the viral genome. Using West Nile virus as a model, we show that this subgenomic RNA is a product of incomplete degradation of viral genomic RNA by cellular ribonucleases. Highly conserved RNA structures located at the beginning of the 3' untranslated region render this RNA resistant to nucleases, and the resulting subgenomic RNA product is essential for virus-induced cytopathicity and pathogenicity. Thus, flaviviruses evolved a unique strategy to generate a noncoding RNA product that allows them to kill the host more efficiently.