RNA 干扰作为哺乳动物抗病毒免疫机制发挥作用。
RNA interference functions as an antiviral immunity mechanism in mammals.
机构信息
Department of Plant Pathology and Microbiology, University of California, Riverside, CA 92521, USA.
出版信息
Science. 2013 Oct 11;342(6155):231-4. doi: 10.1126/science.1241911.
Abstract
Diverse eukaryotic hosts produce virus-derived small interfering RNAs (siRNAs) to direct antiviral immunity by RNA interference (RNAi). However, it remains unknown whether the mammalian RNAi pathway has a natural antiviral function. Here, we show that infection of hamster cells and suckling mice by Nodamura virus (NoV), a mosquito-transmissible RNA virus, requires RNAi suppression by its B2 protein. Loss of B2 expression or its suppressor activity leads to abundant production of viral siRNAs and rapid clearance of the mutant viruses in mice. However, viral small RNAs detected during virulent infection by NoV do not have the properties of canonical siRNAs. These findings have parallels with the induction and suppression of antiviral RNAi by the related Flock house virus in fruit flies and nematodes and reveal a mammalian antiviral immunity mechanism mediated by RNAi.
摘要
不同的真核宿主通过 RNA 干扰（RNAi）产生病毒来源的小干扰 RNA（siRNA），从而指导抗病毒免疫。然而，哺乳动物的 RNAi 途径是否具有天然的抗病毒功能仍不清楚。在这里，我们表明，通过 Nodamura 病毒（NoV）感染仓鼠细胞和乳鼠，该病毒是一种通过蚊子传播的 RNA 病毒，需要其 B2 蛋白抑制 RNAi。B2 表达的丧失或其抑制活性导致大量产生病毒 siRNA，并在小鼠中迅速清除突变病毒。然而，在 NoV 强毒感染过程中检测到的病毒小 RNA 不具有典型 siRNA 的特性。这些发现与相关的 Flock house 病毒在果蝇和线虫中诱导和抑制抗病毒 RNAi 具有相似性，并揭示了一种由 RNAi 介导的哺乳动物抗病毒免疫机制。
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