In summary, HCMV intervenes in the regulation of the three routes of signal transduction characteristic of the UPR, the routes mediated by PERK, IRE1, and ATF6. The HCMV intervention ensures that the virus has time to replicate while the cell is preparing for apoptosis, which leads to cell disruption and the release of viral particles. In this regard, it has been found that the genes encoding ER chaperones are also induced by the virus independently of the ATF6-initiated pathway, possibly because the chaperones are needed for the generation of proteins required by the virus. In parallel, the protein degradation ER degradation-enhancing 1,2-mannosidase-like(EDEM) factor was found to be inhibited, so as to transitorily curtail proteolysis and thus ensure the presence of the molecules necessary for cell survival during viral replication. |