Efficient porcine reproductive and respiratory syndrome virus entry in MARC-145 cells requires EGFR-PI3K-AKT-LIMK1-COFILIN signaling pathway

•Src kinase is involved in PRRSV entry in MARC-145 cells.•EGFR is activated to facilitate PRRSV entry.•Balanced cofilin activity is critical for efficient PRRSV entry.

Viruses have evolved diverse strategies to take over cellular machinery to facilitate their infection. In our studies presented here, we first demonstrated that Src kinase was involved in PRRSV entry in MARC-145 cells. Further studies demonstrated epidermal growth factor receptor (EGFR) was activated by the currently unknown mechanism(s) during PRRSV entry, which subsequently initiated EGFR downstream signal pathways, such as PI3K/AKT/LIMK1. Through these pathways, the virus entry signal was ultimately transferred to cofilin, which might regulate the actin fragmentation and reorganization to facilitate the virus penetration and cytoplasmic trafficking.