Animal virus replication and RNAi-mediated antiviral silencing in Caenorhabditis elegans
Animal virus replication and RNAi-mediated antiviral silencing in Caenorhabditis elegans
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DOI：
10.1038/nature03870
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发表时间：
2005-08-18
期刊：
影响因子：
64.8
通讯作者：
Ding, SW
中科院分区：
文献类型：
--
作者：
Lu, R;Maduro, M;Ding, SW
秀丽隐杆线虫（Caenorhabditis elegans）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），但已知它不支持任何病毒的复制。植物和昆虫编码多种Dicer酶，这些酶识别小rna的不同前体，并可能协同起作用（3-7）。然而，尚不清楚蠕虫和哺乳动物的单个Dicer是否能够像植物(8)和昆虫(9)那样启动小RNA引导的RNA干扰（RNAi）抗病毒免疫。在这里，我们展示了鸟居病毒（FHV）在秀丽隐杆线虫中二分正链RNA基因组的完全复制。研究表明，秀丽隐杆线虫中的FHV复制触发了有效的抗病毒沉默，这种沉默需要RDE-1， RDE-1是一种Argonaute蛋白（10,11），是小干扰rna （sirna）介导的RNAi所必需的，而不是由microrna介导的。这种免疫系统能够在缺乏FHV B2蛋白的情况下快速清除病毒，FHV B2蛋白是rde-1上游的一种广谱RNAi抑制剂（9,12），靶向siRNA前体。这项工作为动物病毒-宿主相互作用的遗传研究建立了秀丽隐杆线虫模型，并表明哺乳动物可能使用siRNA途径作为抗病毒反应。
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.