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The DExD/H-box helicase Dicer-2 mediates the induction of antiviral activity in drosophila

Abstract

Drosophila, like other invertebrates and plants, relies mainly on RNA interference for its defense against viruses. In flies, viral infection also triggers the expression of many genes. One of the genes induced, Vago, encodes a 18-kilodalton cysteine-rich polypeptide. Here we provide genetic evidence that the Vago gene product controlled viral load in the fat body after infection with drosophila C virus. Induction of Vago was dependent on the helicase Dicer-2. Dicer-2 belongs to the same DExD/H-box helicase family as do the RIG-I–like receptors, which sense viral infection and mediate interferon induction in mammals. We propose that this family represents an evolutionary conserved set of sensors that detect viral nucleic acids and direct antiviral responses.

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Figure 1: Vago regulates viral load in the fat body of DCV-infected flies.
Figure 2: Virus-specific transcriptional induction of Vago in wild-type flies.
Figure 3: Fat body–specific transcriptional induction of Vago.
Figure 4: Dicer-2 mediates the induction of Vago expression in DCV-infected flies.
Figure 5: Uncoupling RNA interference and Vago induction.
Figure 6: Protein sequence similarity–based dendrogram of DExD/H-box helicases.

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Acknowledgements

We thank E. Santiago and S. Ozkan for technical expertise; R. Carthew (Northwestern University), J.-M. Reichhart (Unité Propre de Recherché 9022 Centre National de la Recherche Scientifique) and M. Siomi (University of Tokushima) for fly stocks; A. Schneeman (The Scripps Research Institute) for FHV and anti-FHV; D. Ferrandon for critical reading of the manuscript and comments; and E. Levashina for discussions. Confocal microscopy was done at the Strasbourg Esplanade Cellular Imaging Facility (funded by the Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Louis Pasteur University and Alsace Region). Supported by the US National Institutes of Health (PO1 AI070167), Agence Nationale de Recherche Microbiologie-Maladie Emergentes and Centre National de la Recherche Scientifique.

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S.D., N.M., S.M., C.K., D.G.-A., C.D., J.A.H. and J.-L.I. conceived, did and analyzed the experiments; A.B. analyzed the sequences of DExD/H-box helicases; C.A. established and confirmed the identity of transgenic flies expressing FHV B2; and S.D., N.M., J.A.H. and J.-L.I. wrote the manuscript.

Corresponding author

Correspondence to Jean-Luc Imler.

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The authors declare no competing financial interests.

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Deddouche, S., Matt, N., Budd, A. et al. The DExD/H-box helicase Dicer-2 mediates the induction of antiviral activity in drosophila. Nat Immunol 9, 1425–1432 (2008). https://doi.org/10.1038/ni.1664

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