Human Virus-Derived Small RNAs Can Confer Antiviral Immunity in Mammals
Human Virus-Derived Small RNAs Can Confer Antiviral Immunity in Mammals
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DOI：
10.1016/j.immuni.2017.05.006
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发表时间：
2017-06-20
期刊：
影响因子：
32.4
通讯作者：
Zhou, Xi
中科院分区：
文献类型：
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作者：
Qiu, Yang;Xu, Yanpeng;Zhou, Xi
RNA干扰（RNAi）在植物和无脊椎动物中具有强大的抗病毒免疫功能，但RNAi是否在哺乳动物中发挥抗病毒作用仍不清楚。在这里，使用人肠道病毒71（HEV71）作为模型，我们显示HEV71 3A蛋白作为一个真正的病毒抑制剂的RNAi病毒感染过程中。当3A介导的RNAi抑制受损时，突变体HEV71容易触发细胞和小鼠中大量HEV71衍生的具有典型siRNA性质的小RNA的产生。这些病毒衍生的siRNA以Dicer依赖性方式从病毒dsRNA复制中间体产生并加载到AGO中，并且它们在降解同源病毒RNA中具有完全活性。重组HEV71缺乏3A介导的RNAi抑制显着限制在人类体细胞和小鼠，而Dicer缺乏拯救HEV71感染独立于I型干扰素反应。因此，在哺乳动物中，RNAi可以作为由人病毒诱导和抑制的抗病毒免疫起作用。
RNA interference (RNAi) functions as a potent antiviral immunity in plants and invertebrates; however, whether RNAi plays antiviral roles in mammals remains unclear. Here, using human enterovirus 71 (HEV71) as a model, we showed HEV71 3A protein as an authentic viral suppressor of RNAi during viral infection. When the 3A-mediated RNAi suppression was impaired, the mutant HEV71 readily triggered the production of abundant HEV71-derived small RNAs with canonical siRNA properties in cells and mice. These virus-derived siRNAs were produced from viral dsRNA replicative intermediates in a Dicer-dependent manner and loaded into AGO, and they were fully active in degrading cognate viral RNAs. Recombinant HEV71 deficient in 3A-mediated RNAi suppression was significantly restricted in human somatic cells and mice, whereas Dicer deficiency rescued HEV71 infection independently of type I interferon response. Thus, RNAi can function as an antiviral immunity, which is induced and suppressed by a human virus, in mammals.