GCN2 and its downstream activation consequences are part of the signaling pathway called the Integrated Stress Response (ISR), because it integrates cellular responses to diverse stress stimuli such as nutrient deficiency (through GCN2), viral infection (through the double-stranded RNA-dependent protein kinase (PKR)), endoplasmic reticulum stress (through the PKR-like ER kinase (PERK)), and heme deprivation (through heme-regulated eIF2α kinase (HRI)) [29]. Here, EIF2AK3 is linked to viral infectious disease.