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Essential function in vivo for Dicer-2 in host defense against RNA viruses in drosophila

Abstract

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.

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Figure 1: FHV is a drosophila pathogen.
Figure 2: The FHV protein B2 is required for successful viral RNA amplification in flies.
Figure 3: RNAi-mediated resistance of drosophila to infection with FHV.
Figure 4: Dicer-2 mutant flies are more sensitive than wild-type flies to virus infection.
Figure 5: Dicer-2 confers protection of drosophila against infection with SINV.

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Acknowledgements

We thank E. Santiago for technical assistance; S. Ozkan and R. Walther for help with transgenesis; D. Zachary for help with electron microscopy; R. Carthew for Dicer-2 mutant lines; J. Strauss for anti-SINV; J. McCauley for titered stock of SINV; and O. Voinnet for discussions and comments. Supported by Centre National de la Recherche Scientifique, Ministère de la Technologie et de l'Enseignement Supérieur (ACI Microbiologie to J.-L.I.), the National Institutes of Health (GM053491 to A.S.), a Centre National de la Recherche Scientifique post-doctoral fellowship (D.G.A.) and the Ministère de la Recherche du Grand-Duché du Luxembourg (C.D.).

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Supplementary Figure 1

FHV RNA1ΔB2 transgenic flies are protected against a challenge with FHV but not with the unrelated virus DCV. (PDF 15 kb)

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Galiana-Arnoux, D., Dostert, C., Schneemann, A. et al. Essential function in vivo for Dicer-2 in host defense against RNA viruses in drosophila. Nat Immunol 7, 590–597 (2006). https://doi.org/10.1038/ni1335

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