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Animal virus replication and RNAi-mediated antiviral silencing in Caenorhabditis elegans

机译:秀丽隐杆线虫中的动物病毒复制和RNAi介导的抗病毒沉默

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The worm Caenorhabditis elegans is a model system for studying many aspects of biology, including host responses to bacterial pathogens(1,2), but it is not known to support replication of any virus. Plants and insects encode multiple Dicer enzymes that recognize distinct precursors of small RNAs and may act cooperatively(3-7). However, it is not known whether the single Dicer of worms and mammals is able to initiate the small RNA-guided RNA interference (RNAi) antiviral immunity as occurs in plants(8) and insects(9). Here we show complete replication of the Flock house virus (FHV) bipartite, plus-strand RNA genome in C. elegans. We show that FHV replication in C. elegans triggers potent antiviral silencing that requires RDE-1, an Argonaute protein(10,11) essential for RNAi mediated by small interfering RNAs (siRNAs) but not by microRNAs. This immunity system is capable of rapid virus clearance in the absence of FHV B2 protein, which acts as a broad-spectrum RNAi inhibitor(9,12) upstream of rde-1 by targeting the siRNA precursor. This work establishes a C. elegans model for genetic studies of animal virus - host interactions and indicates that mammals might use a siRNA pathway as an antiviral response.
机译:线虫秀丽隐杆线虫是研究生物学许多方面的模型系统,包括宿主对细菌病原体的反应(1,2),但尚不支持任何病毒的复制。植物和昆虫编码多种Dicer酶,这些酶可以识别小RNA的不同前体,并且可以协同作用(3-7)。但是,尚不清楚蠕虫和哺乳动物的单一切丁机是否能够像植物(8)和昆虫(9)一样引发小RNA指导的RNA干扰(RNAi)抗病毒免疫。在这里,我们显示了秀丽隐杆线虫的鸡群病毒(FHV)两方和正链RNA基因组的完全复制。我们表明线虫中的FHV复制触发有效的抗病毒沉默,需要RDE-1,这是一种小干扰RNA(siRNA)介导的RNAi而不是microRNA必需的Argonaute蛋白(10,11)。该免疫系统能够在不存在FHV B2蛋白的情况下快速清除病毒,该蛋白通过靶向siRNA前体充当rde-1上游的广谱RNAi抑制剂(9,12)。这项工作建立了线虫线虫模型,用于动物病毒-宿主相互作用的遗传研究,并表明哺乳动物可能使用siRNA途径作为抗病毒反应。

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