title: Broad RNA interference-mediated antiviral immunity and virus-specific inducible responses in Drosophila.
abstract: The fruit fly Drosophila melanogaster is a good model to unravel the molecular mechanisms of innate immunity and has led to some important discoveries about the sensing and signaling of microbial infections. The response of Drosophila to virus infections remains poorly characterized and appears to involve two facets. On the one hand, RNA interference involves the recognition and processing of dsRNA into small interfering RNAs by the host RNase Dicer-2 (Dcr-2), whereas, on the other hand, an inducible response controlled by the evolutionarily conserved JAK-STAT pathway contributes to the antiviral host defense. To clarify the contribution of the small interfering RNA and JAK-STAT pathways to the control of viral infections, we have compared the resistance of flies wild-type and mutant for Dcr-2 or the JAK kinase Hopscotch to infections by seven RNA or DNA viruses belonging to different families. Our results reveal a unique susceptibility of hop mutant flies to infection by Drosophila C virus and cricket paralysis virus, two members of the Dicistroviridae family, which contrasts with the susceptibility of Dcr-2 mutant flies to many viruses, including the DNA virus invertebrate iridescent virus 6. Genome-wide microarray analysis confirmed that different sets of genes were induced following infection by Drosophila C virus or by two unrelated RNA viruses, Flock House virus and Sindbis virus. Overall, our data reveal that RNA interference is an efficient antiviral mechanism, operating against a large range of viruses, including a DNA virus. By contrast, the antiviral contribution of the JAK-STAT pathway appears to be virus specific.
authors.affiliation: CNRS-UPR9022, Institut de Biologie Moléculaire et Cellulaire, 67084 Strasbourg Cedex, France.
authors.forename: Cordula
authors.initials: C
authors.lastname: Kemp
authors.forename: Stefanie
authors.initials: S
authors.lastname: Mueller
authors.forename: Akira
authors.initials: A
authors.lastname: Goto
authors.forename: Vincent
authors.initials: V
authors.lastname: Barbier
authors.forename: Simona
authors.initials: S
authors.lastname: Paro
authors.forename: François
authors.initials: F
authors.lastname: Bonnay
authors.forename: Catherine
authors.initials: C
authors.lastname: Dostert
authors.forename: Laurent
authors.initials: L
authors.lastname: Troxler
authors.forename: Charles
authors.initials: C
authors.lastname: Hetru
authors.forename: Carine
authors.initials: C
authors.lastname: Meignin
authors.forename: Sébastien
authors.initials: S
authors.lastname: Pfeffer
authors.forename: Jules A
authors.initials: JA
authors.lastname: Hoffmann
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Imler
mesh_terms: D000524:Alphavirus / Q000276:immunology; D018354:Alphavirus Infections / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D000818:Animals; D030801:Animals, Genetically Modified; D004266:DNA Virus Infections / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D029721:Drosophila Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D005786:Gene Expression Regulation; D053612:Janus Kinases / Q000378:metabolism; D008297:Male; D030381:Nodaviridae / Q000276:immunology; D020365:RNA Helicases / Q000235:genetics / Q000276:immunology; D034622:RNA Interference / Q000276:immunology*; D012327:RNA Virus Infections / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D043244:Ribonuclease III / Q000235:genetics / Q000276:immunology; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D014157:Transcription Factors; D053612:Janus Kinases; C085845:hop protein, Drosophila; C478069:DCR-2 protein, Drosophila; D043244:Ribonuclease III; D020365:RNA Helicases