Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life Sciences, Nijmegen Institute for Infection, Inflammation and Immunity, Nijmegen, The Netherlands.
PLoS Pathog. 2012;8(8):e1002872. doi: 10.1371/journal.ppat.1002872. Epub 2012 Aug 16.
RNA interference (RNAi) is a major antiviral pathway that shapes evolution of RNA viruses. We show here that Nora virus, a natural Drosophila pathogen, is both a target and suppressor of RNAi. We detected viral small RNAs with a signature of Dicer-2 dependent small interfering RNAs in Nora virus infected Drosophila. Furthermore, we demonstrate that the Nora virus VP1 protein contains RNAi suppressive activity in vitro and in vivo that enhances pathogenicity of recombinant Sindbis virus in an RNAi dependent manner. Nora virus VP1 and the viral suppressor of RNAi of Cricket paralysis virus (1A) antagonized Argonaute-2 (AGO2) Slicer activity of RNA induced silencing complexes pre-loaded with a methylated single-stranded guide strand. The convergent evolution of AGO2 suppression in two unrelated insect RNA viruses highlights the importance of AGO2 in antiviral defense.
RNA 干扰（RNAi）是一种主要的抗病毒途径，它塑造了 RNA 病毒的进化。我们在这里表明，Nora 病毒，一种天然的果蝇病原体，既是 RNAi 的靶标又是其抑制剂。我们在感染 Nora 病毒的果蝇中检测到了具有 Dicer-2 依赖性小干扰 RNA 特征的病毒小 RNA。此外，我们证明 Nora 病毒 VP1 蛋白在体外和体内具有 RNAi 抑制活性，这种活性以 RNAi 依赖的方式增强了重组 Sindbis 病毒的致病性。Nora 病毒 VP1 和 Cricket 麻痹病毒（1A）的 RNAi 抑制因子拮抗了预先加载有甲基化单链引导链的 RNA 诱导沉默复合物中 Argonaute-2（AGO2）Slicer 的活性。两种不相关的昆虫 RNA 病毒中 AGO2 抑制的趋同进化突出了 AGO2 在抗病毒防御中的重要性。
