One of the most important mechanisms preventing viral replication and dissemination is the apoptosis or programmed cell death, in which infected cells are eradicated through the activation of a group of proenzymes known as caspases. The heat map containing several of the most relevant proteins implicated in apoptosis revealed the induction of multitude of pro-apoptotic genes following pMCV1.4-G860 vaccination, including the initiator caspases Caspase-8 and Caspase-10 and the effector caspases Caspase-6 and Caspase-7, as well as Caspase-1 or Caspase-1A. The injection of the empty plasmid pMCV1.4 was also capable of inducing upregulation of some genes especially implicated in the apoptotic intrinsic pathway. VHSV infection revealed an extensive induction of genes implicated in apoptosis. Thus, all the caspases contained in the microarray were significantly and strongly up-regulated, indicating a powerful activation of the programmed cell death. The profile reflecting the apoptotic induction after viral challenge in pMCV1.4-G860 vaccinated turbot was totally different. Thus, the existence of a specific immune response seems to reduce the viral transcription to a level that practically avoids the activation of the apoptotic mechanisms. Indeed, the caspases analyzed in the microarray were not affected in pMCV1.4-G860 vaccinated fish after VHSV challenge at any of the sampling points. Significant but slight up-regulation in the Gemifloxacin mesylate expression of some specific apoptosis genes was only detected at 24 h. On the other hand, cytotoxic T lymphocytes and natural killer cells are also able to induce cell death through the Perforin/Granzyme-induced apoptosis, in which Perforin and Granulysin generate membrane disruption of virally infected cells and a family of structurally related serine Cantharidin proteases induces apoptosis of the target cell activating the caspases. As it is shown in Fig. 8B, at 72 h after pMCV1.4G860 injection the levels of Granzyme A, Perforin-1 and Antimicrobial peptide NK-lysin were significantly up-regulated, indicating the activation of the cytotoxic cells after viral G glycoprotein expression. As expected, these genes mediating the cytotoxic response were also overexpressed after VHSV administration but, once again, the pattern was very different in previously vaccinated fish, where this effect was practically voided.