Convergent evolution of argonaute-2 slicer antagonism in two distinct insect RNA viruses

PLoS Pathog. 2012;8(8):e1002872. doi: 10.1371/journal.ppat.1002872. Epub 2012 Aug 16.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Argonaute Proteins / genetics
  • Argonaute Proteins / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster
  • Evolution, Molecular*
  • Gene Silencing*
  • Insect Viruses / genetics
  • Insect Viruses / metabolism*
  • RNA Viruses / genetics
  • RNA Viruses / metabolism*

Substances

  • AGO3 protein, Drosophila
  • Argonaute Proteins
  • Drosophila Proteins

Grant support

This work was financially supported by VIDI fellowship (project number 864.08.003), Open Program of the Division for Earth and Life Sciences (project number 821.02.028) from the Netherlands Organization for Scientific Research, and a fellowship from the Nijmegen Centre for Molecular Life Sciences of the Radboud University Nijmegen Medical Centre to RPvR, by grants from the Centre National de la Recherche Scientifiques and from the Agence Nationale de la Recherche (ANR – Nuclear-endosiRNAs) to C.A., and by grants from the Swedish Research Council, the EU 7th Framework Programme, the Swedish Cancer Society, the Academy of Finland and the Sigrid Juselius Foundation to D.H. The Incentive Fund Open Access from the Netherlands Organization for Scientific Research provided support for Open Access publication. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.