The ISR is activated by extrinsic and intrinsic factors such as virus infection and unfolded proteins in the endoplasmic reticulum (ER), respectively, that trigger phosphorylation and inactivation of eukaryotic translation-initiation factor 2 alpha (eIF2α) which shuts down translation and helps restore protein homeostasis (proteostasis). This evidence concerns the gene EIF2A and viral infectious disease.