In mammals, phosphorylation of EIF2α by four dedicated kinases (GCN2, PERK, HRI, and PKR) serves to attenuate the general cytosolic translation in response to a variety of intra- and extracellular stresses (e.g., amino-acid starvation, viral infection, oxidative and unfolded protein stress), and meanwhile stimulates the translation of ATF4, ATF5, and CHOP, the mammalian functional orthologs of ATFS-1, to activate the ISR (Costa-Mattioli and Walter, 2020; Pakos-Zebrucka et al., 2016; Quiros et al., 2017). Here, EIF2AK3 is linked to viral infectious disease.