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* Macrophages et Développement de l’Immunité, Centre National de la Recherche Scientifique, Institut Pasteur, Paris, France;
Virologie et Immunologie Moléculaires, Institut National de la Recherche Agronomique, Jouy-en-Josas, France;
Réseaux Génétiques et Morphodynamiques Cellulaires, Centre National de la Recherche Scientifique-Développement, Evolution, Plasticité du Systéme Nerveux, Institut Alfred Fessard, Gif sur Yvette, France; and
Centre National de la Recherche Scientifique, Université Montpellier II, Montpellier, France
The recent description of virus-induced fish IFNs has raised questions about the evolution of this complex antiviral system. Identification of the receptor of the zebrafish virus-induced IFN (zIFN) was sought to help resolve these questions. We set up an experimental system to study the zIFN system in the course of a viral infection of zebrafish embryos. In this setting, zIFN was induced by viral infection, and we identified zIFN-dependent induced transcripts. Embryos quickly died from the infection, but zIFN overexpression increased their survival. We took advantage of this experimental system to perform in vivo loss and gain of function analysis of candidate receptors of the class II helical receptor family and identified zCRFB1 and zCRFB5 as the two subunits of the zebrafish IFN receptor. Based on the organization of the zIFN gene and the protein structure of the identified receptor components, the virus-induced fish IFNs appear as orthologs of mammalian IFN-
, specifying type III IFN as the ancestral antiviral system of vertebrates.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by GENANIMAL/ANR Project 426.
2 The sequences presented in this article have been submitted to GenBank under accession numbers EF014952 to EF014967.
3 Address correspondence and reprint requests to Dr. Georges Lutfalla, Centre National de la Recherche Scientifique, University Montpellier II CC086, Place Eugene Bataillon, Montpellier, France. E-mail address: lutfalla{at}univ-montp2.fr
4 Abbreviations used in this paper: IFNAR, IFN 
, 
, and omega receptor; IFNGR, IFN-
receptor; IFNLR, IFN- receptor; zIFN, zebrafish virus-induced IFN; VHSV, viral hemorrhagic septicemia virus; SVCV, spring viremia of carp virus; CRFB, class II helical cytokine receptor; EST, expressed sequence tag; hpf, hour postfertilization; zCRFB, zebrafish CRFB; ORF, open reading frame; dpf, day postfertilization; hpi, hour postinfection; hIFNLR1, human IFNLR1.
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