Essential function in vivo for Dicer-2 in host defense against RNA viruses in drosophila.
The fruit fly Drosophila melanogaster is a model system for studying innate immunity, including antiviral host defense. Infection with drosophila C virus triggers a transcriptional response that is dependent in part on the Jak kinase Hopscotch. Here we show that successful infection and killing of drosophila with the insect nodavirus flock house virus was strictly dependent on expression of the viral protein B2, a potent inhibitor of processing of double-stranded RNA mediated by the essential RNA interference factor Dicer. Conversely, flies with a loss-of-function mutation in the gene encoding Dicer-2 (Dcr-2) showed enhanced susceptibility to infection by flock house virus, drosophila C virus and Sindbis virus, members of three different families of RNA viruses. These data demonstrate the importance of RNA interference for controlling virus replication in vivo and establish Dcr-2 as a host susceptibility locus for virus infections.
UPR9022 Centre National de la Recherche Scientifique, Institut de Biologie Moléculaire et Cellulaire Strasbourg 67000, France.
Delphine
D
Galiana-Arnoux
Catherine
C
Dostert
Anette
A
Schneemann
Jules A
JA
Hoffmann
Jean-Luc
JL
Imler
D000818:Animals; D030801:Animals, Genetically Modified; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D009154:Mutation; D030381:Nodaviridae / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020365:RNA Helicases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D012328:RNA Viruses / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D043244:Ribonuclease III; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
D029721:Drosophila Proteins; D012367:RNA, Viral; D014764:Viral Proteins; C478069:DCR-2 protein, Drosophila; D043244:Ribonuclease III; D020365:RNA Helicases