EGFR promotes PEDV internalization via spike protein association and endo−/lysosomal trafficking

Introduction Porcine epidemic diarrhea virus (PEDV) induces severe acute diarrhea, vomit ing, dehydration and high mortality rate in suckling piglets, leading to substantial economic losses for the global swine industry. Previous studies reported that EGFR can promote PEDV infection via modulation of the JAK-STAT type I interferon axis. However, the precise role of EGFR during the early viral entry phase remains unclear. Methods In this study, an EGFR-KO Vero cell line was constructed. Co-immunoprecipitation, viral attachment and internalization assays and confocal colocalization analysis were performed to investigate the role of EGFR in PEDV entry. Results The PEDV spike protein was found to associate with EGFR. EGFR knockout partially impaired viral internalization, whereas viral attachment remained unaffected. Further colocalization analysis showed that PEDV colocalized with EGFR in early endosomes, late endosomes and lysosomes, and that EGFR knockout impaired PEDV colocalization with late endosomes. Discussion EGFR was identified as a host co-factor. It supports PEDV infection by promoting viral internalization and facilitating post-internalization endo−/lysosomal trafficking. This work extends the understanding of coronavirus entry pathways.