Convergent Evolution of Argonaute-2 Slicer Antagonism in Two Distinct Insect RNA Viruses

PLoS Pathogens

Alfred W. Bronkhorst¹  Joël T. van Mierlo¹  Marco Heestermans¹  Gijs J. Overheul¹  Dan Hultmark²  Jens-Ola Ekström²  Sajna A. Sadanandan²  Ronald P. van Rij³  Christophe Antoniewski⁴ 

[1] 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;Department of Molecular Biology, Umeå University, Umeå, Sweden;Drosophila Genetics and Epigenetics, Université Pierre et Marie Curie Paris VI, CNRS UMR 7622 - Biologie du Développement, Paris, France;Institute of Biomedical Technology, University of Tampere, Tampere, Finland

关键词: Small interfering RNAs;    RNA interference;    Drosophila melanogaster;    dsRNA viruses;    Genomic libraries;    Recombinant proteins;    Invertebrate genomics;    Viral genomics;   

DOI  :  10.1371/journal.ppat.1002872

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY