Convergent evolution of argonaute-2 slicer antagonism in two distinct insect RNA viruses.
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.
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.
Joël T
JT
van Mierlo
Alfred W
AW
Bronkhorst
Gijs J
GJ
Overheul
Sajna A
SA
Sadanandan
Jens-Ola
JO
Ekström
Marco
M
Heestermans
Dan
D
Hultmark
Christophe
C
Antoniewski
Ronald P
RP
van Rij
D000818:Animals; D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D019143:Evolution, Molecular; D020868:Gene Silencing; D007304:Insect Viruses / Q000235:genetics / Q000378:metabolism*; D012328:RNA Viruses / Q000235:genetics / Q000378:metabolism*
C518392:AGO3 protein, Drosophila; D060565:Argonaute Proteins; D029721:Drosophila Proteins