The ISR induces phosphorylation of eukaryotic initiation factor subunit alpha (eIF2α), and activation of the Atf4 axis, through four upstream kinases; HRI (eIF2α kinase heme‐regulated inhibitor), GCN2 (general control nonderepressible 2), PKR (double‐stranded RNA [dsRNA]‐dependent protein kinase) and PERK, in response to hypoxia, nutrient deprivation, viral infection, and oxidative stress, respectively (Wek et al., 2006). This evidence concerns the gene EIF2AK3 and viral infectious disease.