RIG-I Recognizes the 5′ Region of Dengue and Zika Virus Genomes
RIG-I Recognizes the 5′ Region of Dengue and Zika Virus Genomes
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DOI：
10.1016/j.celrep.2018.06.047
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发表时间：
2018-07-10
期刊：
影响因子：
8.8
通讯作者：
Jouvenet, Nolwenn
中科院分区：
文献类型：
--
作者：
Chazal, Maxime;Beauclair, Guillaume;Jouvenet, Nolwenn
黄病毒属包括主要的人类病原体，如登革热（DENV）和寨卡（ZIKV）病毒。RIG-I和MDA 5是参与检测病毒RNA的关键细胞质病原体识别受体。在这里，我们表明在DENV感染期间与RIG-I共纯化的RNA是免疫刺激性的，而与MDA 5结合的RNA不是。结合下一代测序（NGS）的亲和纯化方法揭示了DENV基因组的5'区域被RIG-I识别。没有DENV RNA与MDA 5结合。DENV基因组片段的体外产生证实了NGS数据，并揭示了基因组的5'端，当携带5'-三磷酸时，是RIG-I配体。ZIKV基因组的5'区也是RIG-I激动剂。我们认为RIG-I在加帽前与黄病毒新生转录物的高度结构化和保守的5'区结合，并且这种机制导致受感染细胞分泌干扰素。
The flavivirus genus comprises major human pathogens, such as Dengue (DENV) and Zika (ZIKV) viruses. RIG-I and MDA5 are key cytoplasmic pathogen recognition receptors that are implicated in detecting viral RNAs. Here, we show that RNAs that co-purified with RIG-I during DENV infection are immuno-stimulatory, whereas RNAs bound to MDA5 are not. An affinity purification method combined with next-generation sequencing (NGS) revealed that the 5' region of the DENV genome is recognized by RIG-I. No DENV RNA was bound to MDA5. In vitro production of fragments of the DENV genome confirmed the NGS data and revealed that the 5' end of the genome, when bearing 5'-triphosphates, is the RIG-I ligand. The 5' region of the ZIKV genome is also a RIG-I agonist. We propose that RIG-I binds to the highly structured and conserved 5' region of flavivirus nascent transcripts before capping and that this mechanism leads to interferon secretion by infected cells.