López-Muñoz, A., Roca, F.J., Sepulcre, M.P., Meseguer, J., and Mulero, V. (2010) Zebrafish Larvae Are Unable To Mount a Protective Antiviral Response Against Waterborne Infection by Spring Viremia of Carp Virus. Developmental and comparative immunology. 34(5):546-552.
Interferons (IFNs) and their receptors exist in all classes of vertebrates, where they represent early elements in innate and adaptive immunity. Both types I and II IFNs have been discovered in fish and type I IFN has recently been classified into two groups based on their primary protein sequences and biological activities. Thus, although group I and II zebrafish IFN show powerful antiviral activities, only group I (IFNvarphi1) is able to protect the fish against bacterial infection. In addition, group II IFNs (IFNvarphi2 and IFNvarphi3) induce a rapid and transient expression of antiviral genes, while group I IFN exerts a slow but more powerful induction of several antiviral and pro-inflammatory genes. To gain further insight into the IFN system of fish, we have developed a waterborne infection model of zebrafish larvae with the spring viremia of carp virus (SVCV). Larvae were challenged 3 days post-fertilization by immersion, which considerably reduces the manipulation of fish and represents a more natural route of infection. Using this infection model, we unexpectedly found an inability on the part of zebrafish larvae to mount a protecting antiviral response to waterborne SVCV. Nevertheless, zebrafish larvae showed a functional antiviral system since ectopic expression of the cDNA of both groups I and II IFN was able to protect them against SVCV via the induction of IFN-stimulated genes (ISGs). Interestingly, group II IFNs also induced group I IFN, suggesting crosstalk between these two kinds of antiviral IFN. These results further confirm the antiviral activities of type I IFN in the zebrafish and provide the first viral infection model for zebrafish larvae using a natural route of infection. This model, in combination with the powerful gene overexpression and morpholino-mediated knockdown techniques, will help to illuminate the IFN system of teleost fish.