title: The two groups of zebrafish virus-induced interferons signal via distinct receptors with specific and shared chains.
abstract: Because the availability of fish genomic data, the number of reported sequences for fish type II helical cytokines is rapidly growing, featuring different IFNs including virus-induced IFNs (IFNphi) and IFN-gamma, and IL-10 with its related cytokines (IL-20, IL-22, and IL-26). Many candidate receptors exist for these cytokines and various authors have postulated which receptor chain would be involved in which functional receptor in fish. To date, only the receptor for zebrafish IFNphi1 has been identified functionally. Three genes encoding virus-induced IFNphis have been reported in zebrafish. In addition to these genes clustered on chromosome 3, we have identified a fourth IFNphi gene on chromosome 12. All these genes possess the intron-exon organization of mammalian lambda IFNs. In the zebrafish larva, all induce the expression of reporter antiviral genes; protection in a viral challenge assay was observed for IFNphi1 and IFNphi2. Using a combination of gain- and loss-of-function experiments, we also show that all zebrafish IFNphis do not bind to the same receptor. Two subgroups of fish virus-induced IFNs have been defined based on conserved cysteines, and we find that this subdivision correlates with receptor usage. Both receptor complexes include a common short chain receptor (CRFB5) and a specific long chain receptor (CRFB1 or CRFB2).
authors.affiliation: Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques, Montpellier, France.
authors.forename: Dina
authors.initials: D
authors.lastname: Aggad
authors.forename: Martine
authors.initials: M
authors.lastname: Mazel
authors.forename: Pierre
authors.initials: P
authors.lastname: Boudinot
authors.forename: Knud Erik
authors.initials: KE
authors.lastname: Mogensen
authors.forename: Ole Jensen
authors.initials: OJ
authors.lastname: Hamming
authors.forename: Rune
authors.initials: R
authors.lastname: Hartmann
authors.forename: Sergei
authors.initials: S
authors.lastname: Kotenko
authors.forename: Philippe
authors.initials: P
authors.lastname: Herbomel
authors.forename: Georges
authors.initials: G
authors.lastname: Lutfalla
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Levraud
mesh_terms: D000818:Animals; D002875:Chromosomes; D017124:Conserved Sequence; D003545:Cysteine; D016207:Cytokines; D040461:Gene Components; D007372:Interferons / Q000235:genetics / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D017471:Receptors, Interferon / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D014780:Viruses / Q000276:immunology*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C586448:CRFB1 protein, zebrafish; D016207:Cytokines; D017471:Receptors, Interferon; D029961:Zebrafish Proteins; C543714:inteferon phi2, zebrafish; C543713:interferon phi1, zebrafish; D007372:Interferons; D003545:Cysteine