RNA-based viral immunity initiated by the Dicer family of host immune receptors.
RNA-based viral immunity initiated by the Dicer family of host immune receptors.
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DOI：
10.1111/j.1600-065x.2008.00722.x
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发表时间：
2009-01
影响因子：
8.7
通讯作者：
Ding SW
中科院分区：
文献类型：
--
作者：
Aliyari R;Ding SW
20世纪90年代初，在植物中首次报道了RNA以核苷酸序列同源性依赖的方式抑制病毒感染。过去15年的研究已经建立了一种全新的基于RNA的针对病毒的免疫系统，该系统机械地位于美国加利福尼亚州的河滨。与RNA沉默或RNA干扰(RNAi)相关。这种病毒免疫始于宿主免疫受体的DICER核酸酶家族识别病毒双链或结构的RNA。在真菌、植物和无脊椎动物中，病毒RNA触发器被加工成小干扰RNA(SiRNAs)，通过类似RNAseH的ArgAerte蛋白引导同源病毒基因组和/或信使RNA的特异性沉默。病毒来源的siRNAs的深度测序表明，对正链RNA基因组的病毒的免疫是由病毒后代(+)RNA合成启动过程中形成的dsRNA识别所诱导的。这些生物中基于RNA的免疫途径与RNAi的典型dsRNA-siRNA途径重叠，可能需要植物和线虫中依赖宿主RNA的RNA聚合酶扩增病毒siRNAs。在感染了RNA病毒的哺乳动物细胞中，无法检测到病毒衍生的小RNA的产生。然而，感染几种核复制DNA病毒的哺乳动物可以诱导产生病毒衍生的microRNAs，该microRNAs能够沉默宿主和病毒mRNAs，就像病毒siRNAs一样。值得注意的是，最近的研究表明，原核生物还会产生病毒衍生的小RNA，称为CRISPR RNAs，以指导抗病毒防御，但其方式尚未确定。本文综述了小RNA介导的病毒免疫的关键成分，包括病毒感受器、病毒触发物、效应器和扩增器的识别和机制的最新进展。我们还强调了许多悬而未决的问题中的一些。
Suppression of viral infection by RNA in a nucleotide sequence homology-dependent manner was first reported in plants in early 1990s. Studies in the past 15 years have established a completely new RNA-based immune system against viruses that is mechanistically Riverside, CA, USA. related to RNA silencing or RNA interference (RNAi). This viral immunity begins with recognition of viral double-stranded or structured RNA by the Dicer nuclease family of host immune receptors. In fungi, plants and invertebrates, the viral RNA trigger is processed into small interfering RNAs (siRNAs) to direct specific silencing of the homologous viral genomic and/or messenger RNAs by an RNaseH-like Argonaute protein. Deep sequencing of virus-derived siRNAs indicates that the immunity against viruses with a positive-strand RNA genome is induced by Dicer recognition of dsRNA formed during the initiation of viral progeny (+)RNA synthesis. The RNA-based immune pathway in these organisms overlaps the canonical dsRNA-siRNA pathway of RNAi and may require amplification of viral siRNAs by host RNA-dependent RNA polymerase in plants and nematodes. Production of virus-derived small RNAs is undetectable in mammalian cells infected with RNA viruses. However, infection of mammals with several nucleus-replicating DNA viruses induces production of virus-derived microRNAs capable of silencing host and viral mRNAs as found for viral siRNAs. Remarkably, recent studies indicate that prokaryotes also produce virus-derived small RNAs known as CRISPR RNAs to guide antiviral defense in a manner that has yet to be defined. In this article, we review the recent progress on the identification and mechanism of the key components including viral sensors, viral triggers, effectors, and amplifiers, of the small RNA-directed viral immunity. We also highlight some of the many unresolved questions.