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* Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques, Montpellier, France;
Université Montpellier, Montpellier, France;
Virologie et Immunologie Moléculaires, Institut National de la Recherche Agronomique, Jouy-en-Josas, France;
Centre for Structural Biology, Department of Molecular Biology, University of Aarhus, Aarhus, Denmark;
¶ Department of Biochemistry and Molecular Biology, University Hospital Cancer Center, New Jersey Medical School, Newark, NJ 07103;
|| Macrophages et Développement de l’Immunité, Institut Pasteur, Paris, France; and
# Centre National de la Recherche Scientifique, Paris, France
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 (IFN
) and IFN-
, 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 IFN1 has been identified functionally. Three genes encoding virus-induced IFNs have been reported in zebrafish. In addition to these genes clustered on chromosome 3, we have identified a fourth IFN gene on chromosome 12. All these genes possess the intron-exon organization of mammalian 
IFNs. In the zebrafish larva, all induce the expression of reporter antiviral genes; protection in a viral challenge assay was observed for IFN1 and IFN2. Using a combination of gain- and loss-of-function experiments, we also show that all zebrafish IFNs 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).
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 funded by grants from Agence Nationale pour la Recherche (MIME2007), Institut Pasteur, and Institut National de la Recherche Agronomique (PTR231). O.J.H. was supported by The Danish Cancer Society (Grant no: 95095721). R.H. was supported by a Novo Nordisk Foundation senior research grant and by grants from The Danish Medical Research Council (Grant no: 22-04-0704), The Carlsberg Foundation, and an Arne Hansen stipend. S.K. was supported by the U.S. Public Health Services (Grant R01 AI057468 from the National Institute of Allergy and Infectious Diseases).
2 Address correspondence and reprint requests to Georges Lutfalla, UMR5235, DAA, cc86, CNRS, Place Eugène Bataillon, Montpellier, France or Jean-Pierre Levraud, Institut Pasteur, 25 rue du Dr. Roux, Paris, France. E-mail addresses: lutfalla{at}univ-montp2.fr or jean-pierre.levraud{at}pasteur.fr
3 Abbreviations used in this paper: SVCV, spring viremia of carp virus; IHNV, infectious haemorrhagic necrosis virus; ORF, open reading frame; hpf, hours post fertilization; hpvc, hours post viral challenge; Q-RT-PCR, quantitative RT-PCR.
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