Mammals have four such kinases: GCN2, PERK, HRI, and PKR, which are activated in response to nutrient deprivation, ER stress, cytoplasmic protein misfolding, and viral infection, respectively, while budding yeast has only one, Gcn2.16–18 Upon phosphorylation, eIF2 becomes a competitive inhibitor of its own guanine exchange factor (GEF) eIF2B,19,20 preventing the exchange of GDP for GTP, binding of initiator methionyl tRNA, and its participation in a new round of initiation. This evidence concerns the gene EIF2AK4 and viral infectious disease.