ATF6 and viral infectious disease: Physiological and pathological stimuli, such as serum-starved conditions, high protein demand, viral infections, and inflammatory cytokines, can disrupt ER homeostasis resulting in an accumulation of misfolded proteins.10 To mitigate ER stress, cells activate the unfolded protein response (UPR), which is regulated by three major pathways, each with its own initiator: protein kinase RNA-like ER kinase (PERK); activating transcription factor 6 (ATF6); or inositol-requiring enzyme 1α (IRE1α).