Fig. 5.

The cross-talks between three UPR branches and temporal control of UPR during coronavirus infection, using IBV as an example. At the early stage (1–8 h) of infection, the PERK/PKR triggers translational block by eIF2α phosphorylation. The activation of ATF4 and its downstream signaling leads to translation recovery and accumulation of CHOP. The ATF6 and IRE1 branches possibly activate at a much later time of IBV infection (12–16 h). Enhanced ER folding and activation of ERAD may promote adaptation to the ER stress and cell survival. Finally, prolonged ER stress due to continuous IBV replication and budding led to the dead phase of UPR, characterized by caspase cleavage and other apoptosis mediated cell demolitions.