In unstressed conditions, GRP78 binds to and sequesters three UPR regulatory proteins, PERK, ATF6, and IreI, and upon the induction of ER stress by a number of mechanisms including viral infection, PERK, ATF6, and IreI are released from GRP78 leading to the transcriptional regulation of a number of stress response genes [27–29]. This evidence concerns the gene EIF2AK3 and viral infectious disease.