IRF3 and IRF7 were also affected by the vaccine at the same time point. Moreover, some genes related with the activity of the transcription factor NF-kappa-B, such as the activator IKKbeta or the NF-kappa-B inhibitor zeta, were significantly down-regulated by pMCV1.4-G860. TLR2 recognize other viral components such as envelope glycoproteins and, although no significant up-regulations were observed for this gene after vaccination, the heat map reflects a slight induction. TLR2 activation induces apoptosis through a FADD/Caspase 8 pathway and both genes appeared overrepresented at 72 h, revealing a possible stimulation of the TLR pathway via TLR2 and ultimately, inducing apoptosis. With regard to the viral challenge, it is interesting to highlight that some Toll-like receptors with a typical role in bacterial component detection have been found to be strongly regulated after VHSV infection, and this Acetohydroxamic acid induction could suggest a novel role of these receptors in the recognition of viral components. A sequence annotated as TLR13 was also modulated at 24 h; there is little information about the function of this receptor and the nature of their ligands remains still poorly Notopterol understood, but there are evidences about the recognition of bacterial rRNA as well as vesicular stomatitis virus by TLR13. As was expected, the typical viral-recognition receptors TLR3 and TLR8 were significantly up-regulated after VHSV challenge. Focusing the attention in the downstream signalling components, a pronounced induction of several proteins was observed. Some molecules were also found to be down-regulated, including inhibitors of the transcription factor NF-kappa-B as well as numerous molecules implicated in their activation, possibly due to the maintenance of equilibrium in the NF-kappa-B activity. On the other hand, VHSV infection in vaccinated fish revealed a completely different pattern, even TLR2 and TLR5 were found to be significantly downregulated at 24 h and the other TLRs were not affected by the viral infection. As a consequence, the induction of downstream proteins was practically suppressed or down-regulated and only in the case of IRF3 and IRF7 significant up-regulations were detected at 24 h, with a return to the basal levels at 72 h.