In addition to dsRNA detection, different stress signals trigger eIF2a phosphorylation, thus attenuating mRNA translation and activating gene expression programs known globally as the integrated stress response (ISR) [37] . To date, four kinases have been identified to mediate eIF2a phosphorylation: PKR, PERK (protein kinase RNA (PKR)-like ER kinase) [38] , GCN2 (general control non-derepressible-2) [39, 40] and HRI (heme-regulated inhibitor) [41, 42] . ER stress-mediated eIF2a phosphorylation is carried out by PERK, which is activated by an excess of unfolded proteins accumulating in the ER lumen [38] . Activated PERK phosphorylates eIF2a, attenuating protein synthesis and triggering the translation of specific molecules such as the transcription factor ATF4, which is necessary to mount part of a particular ISR, known as the unfolded protein response (UPR) [43, 44] . Interestingly DNA viruses, such as HSV, that use the ER as a part of its replication cycle, have been reported to interfere with the ER stress response through different mechanisms, such as the dephosphorylation of eIF2a by the viral phosphatase 1 activator, ICP34.5 [45, 46] .