The interferon system is an early antiviral immune process controlling most virus infections in the absence of specific immunity, buying time for the generation of adaptive defense mechanisms. Nowadays is well known that fish type I IFNs induce the expression of a wide variety of IFNstimulated genes after Sanggenone-C recognition of specific IFN receptors. These ISGs reduce the viral replication and dissemination through different blocking mechanisms. Two type I IFNs, annotated as ����Interferon phi 2���� and ����Interferon alpha 2 precursor����, as well as some of the most relevant IFN-related sequences modulated in the microarray were analyzed in the different groups. Recently these two turbot type I IFNs were characterized and renamed as Ifn1 and Ifn2, respectively. No up-regulations were detected in the level of any of both IFNs after vaccination, and even Interferon alpha 2 precursor was significantly down-regulated in comparison with control fish. However, Interferon regulatory factors and the majority of ISGs were up-regulated after 72 h. The most induced ISG by pMCV1.4-G860 was Mx, followed by Interferon-inducible protein 56 and IFI56, two genes or different parts of the same gene belonging to the IFIT family. These up-regulations in downstream genes revealed an activation of the IFN signalling pathway after immunization with pMCV1.4-G860 even when no up-regulations in the expression of IFNs were observed. After viral infection a remarkable induction of these genes was Indinavir sulfate observed with some exception. Thus, Interferon phi 2 was highly up-regulated especially at 72 h, whereas Interferon alpha 2 precursor transcription was down-regulated. Interestingly, we previously observed that both turbot IFNs were overexpressed after VHSV challenge although at different level, being Ifn1 strongly induced and Ifn2 slightly up-regulated and with a brief induction time. Nevertheless, an overall and strong up-regulation of ISGs was observed. There are evidences suggesting that different forms of type I IFNs may have complementary antiviral activities in different cells, at different stages of infection or differ functionally, and this was also observed for turbot type I IFNs. Whereas Ifn1 showed a typical antiviral activity, Ifn2 was no able to increase the expression of ISGs and therefore, did not show any protective effect against VHSV, but was able to up-regulate the level of several immune-related genes, including pro-inflammatory cytokines.