Figure 1

Three UPR signalling pathways driven by ERS in response to animal viral infections. Accumulating misfolded or unfolded proteins in the ER lumen cause ERS, followed by activation of the typical UPRs to relieve ERS. Dissociation from BiP leads to the activation of three ER transmembrane protein sensors: PERK, IRE1, and ATF6. For the PERK signalling pathway, PERK first undergoes phosphorylation and dimerization, followed by phosphorylation of eIF2α. p-eIF2α can extensively inhibit intracellular protein translation but can selectively enhance the expression of ATF4, which can activate CHOP expression and promote the expression of UPR genes and ERAD components. For the IRE1 signalling pathway, phosphorylation and dimerization of IRE1 not only lead to the excision of XBP1 mRNA to form the mature form of XBP1s, which translocates to the nucleus and promotes expression of the UPR genes and ERAD components but also selectively promote apoptosis through the JNK-caspase12 pathway or directly promotes mRNA degradation through RIDD. ATF6 translocates to the Golgi and is cleaved to form cleaved ATF6(N), which enters the nucleus and binds on the ERSE to promote the expression of BiP, XBP1, CHOP, and ERAD components. A substantial number of animal viruses induce ERS in infected host cells. The ERS-driven UPR either inhibits or promotes viral proliferation. Black and blue pointed arrows denote activation, and black and blue blunt-end arrows denote inhibition. A ★ in the figure represents differences in the molecular mechanisms and regulation of viral replication caused by the same animal viruses. For example, JEV infection with BV2 cells activates the PERK and IRE1 pathways (marked as this in the figure), but infection with SH-SY5Y cells only activates the PERK pathway. ST cells, immune and non-immune organs infected with CSFV activate the three UPR pathways (marked as this in the figure), but CSFV infection with PK-15 cells slightly inhibits the ATF6 pathway.