title: Both STING and MAVS fish orthologs contribute to the induction of interferon mediated by RIG-I.
abstract: Viral infections are detected in most cases by the host innate immune system through pattern-recognition receptors (PRR), the sensors for pathogen-associated molecular patterns (PAMPs), which induce the production of cytokines, such as type I interferons (IFN). Recent identification in mammalian and teleost fish of cytoplasmic viral RNA sensors, RIG-I-like receptors (RLRs), and their mitochondrial adaptor: the mitochondrial antiviral signaling (MAVS) protein, also called IPS-1, highlight their important role in the induction of IFN at the early stage of a virus infection. More recently, an endoplasmic reticulum (ER) adaptor: the stimulator of interferon genes (STING) protein, also called MITA, ERIS and MPYS, has been shown to play a pivotal role in response to both non-self-cytosolic RNA and dsDNA. In this study, we cloned STING cDNAs from zebrafish and showed that it was an ortholog to mammalian STING. We demonstrated that overexpression of this ER protein in fish cells led to a constitutive induction of IFN and interferon-stimulated genes (ISGs). STING-overexpressing cells were almost fully protected against RNA virus infection with a strong inhibition of both DNA and RNA virus replication. In addition, we found that together with MAVS, STING was an important player in the RIG-I IFN-inducing pathway. This report provides the demonstration that teleost fish possess a functional RLR pathway in which MAVS and STING are downstream signaling molecules of RIG-I. The Sequences presented in this article have been submitted to GenBank under accession numbers: Zebrafish STING (HE856619); EPC STING (HE856620); EPC IRF3 (HE856621); EPC IFN promoter (HE856618).
authors.affiliation: Unité de Virologie et d'Immunologie Moléculaires, INRA, CRJ, Jouy-en-Josas, France. stephane.biacchesi@jouy.inra.fr
authors.forename: Stéphane
authors.initials: S
authors.lastname: Biacchesi
authors.forename: Emilie
authors.initials: E
authors.lastname: Mérour
authors.forename: Annie
authors.initials: A
authors.lastname: Lamoureux
authors.forename: Julie
authors.initials: J
authors.lastname: Bernard
authors.forename: Michel
authors.initials: M
authors.lastname: Brémont
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D004267:DNA Viruses / Q000276:immunology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005393:Fish Diseases / Q000235:genetics / Q000276:immunology / Q000821:virology; D005399:Fishes / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015870:Gene Expression; D005786:Gene Expression Regulation; D007372:Interferons / Q000096:biosynthesis*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D011485:Protein Binding; D021381:Protein Transport; D012328:RNA Viruses / Q000276:immunology; D016415:Sequence Alignment; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology / Q000821:virology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; D007372:Interferons; D053487:DEAD-box RNA Helicases