PERK-eIF2α activation by avian reticuloendotheliosis virus: a dual strategy to suppress apoptosis and aggravate immunosuppression for enhanced replication.

Viral infection induces endoplasmic reticulum stress (ERS) and the subsequent unfolded protein response (UPR), which play a pivotal role in viral replication and pathogenesis. However, the specific implications of ERS in REV infection remain poorly defined. In this study, we demonstrate that reticuloendotheliosis virus (REV) infection induces significant endoplasmic reticulum (ER) swelling and upregulates the expression of the ERS marker HSPA5 in DF-1 cells. By modulating ERS, we found that the ERS activation significantly promoted REV replication. Further investigation reveals that among the UPR signaling pathways, the PERK branch was specifically activated in REV-infected cells, as indicated by a significant increase in phosphorylated PERK and its downstream target, eukaryotic translation initiation factor 2α (eIF2α). We subsequently established that activation of the PERK-eIF2α signaling axis promotes REV replication. Concurrently, REV-triggered PERK-eIF2α activation attenuated apoptotic cell death and exacerbated immunosuppression. In conclusion, this study demonstrates that REV infection induces ERS in DF-1 cells, leading to specific activation of the PERK-eIF2α signaling axis. The PERK-mediated response facilitates viral replication by simultaneously suppressing apoptosis and aggravating immunosuppression.