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Department of Cell Biology and Histology, Faculty of Biology, University of Murcia, Murcia, Spain
The IFNs and their receptors have existed in early chordates for 
500 million years and represent the early elements in innate and adaptive immunity. Both types I and II IFNs have been discovered in fish, and type I has recently been classified into two groups based on their primary protein sequences. However, the biological activities of fish IFNs and their roles in infection are largely unknown. Using the zebrafish and manageable bacterial (Streptococcus iniae) and viral (spring viremia of carp virus) infection models, we are reporting in this study that zebrafish IFN (zfIFN) 
failed to induce antiviral and proinflammatory genes when administered in vivo, which correlates with its inability to protect the fish against bacterial and viral infections. We also found that, although both group I (i.e., zfIFN1) and group II zfIFNs (i.e., zfIFN2 and zfIFN3) displayed strong in vivo antiviral activities, only group I zfIFN was able to protect the fish against bacterial infection, which may reflect the different patterns and kinetics of immune-related genes elicited by these two groups of IFNs. Thus, group II zfIFNs induced a rapid and transient expression of antiviral genes, whereas group I zfIFN exerted a slow but more powerful induction of several antiviral and proinflammatory genes. Collectively, our results suggest nonredundant, complementary roles of type I zfIFNs in viral infections and provide evidence for a pivotal role of the recently identified group II IFN of fish in the early stages of viral infections.
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 has been supported by the Spanish Ministry of Education and Science (Grants BIO2005-05078 and CSD2007-00002), the Fundación Séneca-Murcia (Grant 04538/GERM/06), the Fundación Marcelino Botín, and the University of Murcia (fellowships to A.L.-M.).
2 Address correspondence and reprint requests to Dr. Victoriano Mulero, Department of Cell Biology and Histology, Faculty of Biology, University of Murcia, 30100 Murcia, Spain. E-mail address: vmulero{at}um.es
3 Abbreviations used in this paper: Mx, myxovirus (influenza virus) resistance; dpi, days postinjection; EPC, epithelioma papulosum cyprinid; hpi, hours postinjection; NOS, NO synthase; PKZ, protein kinase containing Z-DNA binding domain; SVCV, spring viremia of carp virus; TCID, 50% tissue culture infection dose; zfIFN, zebrafish IFN.
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