title: Cytokine Diedel and a viral homologue suppress the IMD pathway in Drosophila.
abstract: Viruses are obligatory intracellular parasites that suffer strong evolutionary pressure from the host immune system. Rapidly evolving viral genomes can adapt to this pressure by acquiring genes that counteract host defense mechanisms. For example, many vertebrate DNA viruses have hijacked cellular genes encoding cytokines or cytokine receptors to disrupt host cell communication. Insect viruses express suppressors of RNA interference or apoptosis, highlighting the importance of these cell intrinsic antiviral mechanisms in invertebrates. Here, we report the identification and characterization of a family of proteins encoded by insect DNA viruses that are homologous to a 12-kDa circulating protein encoded by the virus-induced Drosophila gene diedel (die). We show that die mutant flies have shortened lifespan and succumb more rapidly than controls when infected with Sindbis virus. This reduced viability is associated with deregulated activation of the immune deficiency (IMD) pathway of host defense and can be rescued by mutations in the genes encoding the homolog of IKKγ or IMD itself. Our results reveal an endogenous pathway that is exploited by insect viruses to modulate NF-κB signaling and promote fly survival during the antiviral response.
authors.affiliation: Institut de Biologie Moleculaire et Cellulaire, CNRS-Unité Propre de Recherche 9022, 67084 Strasbourg, France;
authors.forename: Olivier
authors.initials: O
authors.lastname: Lamiable
authors.affiliation: Architecture et Fonction des Macromolécules Biologiques, CNRS and Université Aix-Marseille, Unité Mixte de Recherche 7257, 13288 Marseille, France;
authors.forename: Christine
authors.initials: C
authors.lastname: Kellenberger
authors.affiliation: Institut de Biologie Moleculaire et Cellulaire, CNRS-Unité Propre de Recherche 9022, 67084 Strasbourg, France;
authors.forename: Cordula
authors.initials: C
authors.lastname: Kemp
authors.affiliation: Institut de Biologie Moleculaire et Cellulaire, CNRS-Unité Propre de Recherche 9022, 67084 Strasbourg, France;
authors.forename: Laurent
authors.initials: L
authors.lastname: Troxler
authors.affiliation: Department of Cell and Molecular Biology, Division of Signaling and Functional Genomics and University of Heidelberg, Medical Faculty Mannheim, German Cancer Research Center, 69120 Heidelberg, Germany;
authors.forename: Nadège
authors.initials: N
authors.lastname: Pelte
authors.affiliation: Department of Cell and Molecular Biology, Division of Signaling and Functional Genomics and University of Heidelberg, Medical Faculty Mannheim, German Cancer Research Center, 69120 Heidelberg, Germany;
authors.forename: Michael
authors.initials: M
authors.lastname: Boutros
authors.affiliation: Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CEP30270-901 Belo Horizonte, Brazil;
authors.forename: Joao Trindade
authors.identifier: http://orcid.org/0000-0002-3457-3320
authors.initials: JT
authors.lastname: Marques
authors.affiliation: Institut de Biologie Moleculaire et Cellulaire, CNRS-Unité Propre de Recherche 9022, 67084 Strasbourg, France;
authors.forename: Laurent
authors.initials: L
authors.lastname: Daeffler
authors.affiliation: Institut de Biologie Moleculaire et Cellulaire, CNRS-Unité Propre de Recherche 9022, 67084 Strasbourg, France; University of Strasbourg Institute for Advanced Studies, Université de Strasbourg, 67084 Strasbourg, France;
authors.forename: Jules A
authors.initials: JA
authors.lastname: Hoffmann
authors.affiliation: Architecture et Fonction des Macromolécules Biologiques, CNRS and Université Aix-Marseille, Unité Mixte de Recherche 7257, 13288 Marseille, France;
authors.forename: Alain
authors.initials: A
authors.lastname: Roussel
authors.affiliation: Institut de Biologie Moleculaire et Cellulaire, CNRS-Unité Propre de Recherche 9022, 67084 Strasbourg, France; University of Strasbourg Institute for Advanced Studies, Université de Strasbourg, 67084 Strasbourg, France; Faculté des Sciences de la Vie, Université de Strasbourg, 67083 Strasbourg, France jl.imler@unistra.fr.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Imler
mesh_terms: D018354:Alphavirus Infections / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D016207:Cytokines / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D007109:Immunity / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D012845:Sindbis Virus; D016019:Survival Analysis; D015854:Up-Regulation / Q000235:genetics
chemical_list: D016207:Cytokines; C000608275:Diedel protein, Drosophila; D029721:Drosophila Proteins
keywords: Edin; Sindbis virus; antiviral immunity; cytokine; virokine