Cellular stressors, such as viral infection, misfolded proteins and amino acid starvation, can activate the ISR through one of four kinases (interferon-induced double-stranded RNA-dependent eIF2α kinase [PKR], endoplasmic reticulum [ER]-resident kinase [PERK], general control non-derepressible 2 [GCN2], or heme-regulated inhibitor kinase [HRI]), that all phosphorylate eIF2α at serine 51 (Fig. 3a)29, 33. This evidence concerns the gene EIF2AK1 and viral infectious disease.