Metalloprotease ADAM17 regulates porcine epidemic diarrhea virus infection by modifying aminopeptidase N

Porcine epidemic diarrhea virus (PEDV) is a causative agent of porcine epidemic diarrhea (PED). PED, characterized by acute diarrhea, vomiting, dehydration, has caused serious economic losses in pig industry worldwide. Here, we demonstrate that activation of a disintergrin and metalloprotease 17 (ADAM17) induced the decrease of PEDV infection in HEK293 and IPEC-J2 cells and the downregulation of cell surface aminopeptidase N (APN) expression, an important entry factor for PEDV infection. Furthermore, overexpression of ADAM17 suppressed PEDV infection in HEK293 and IPEC-J2 cells, whereas ablation of ADAM17 expression using ADAM17 specific siRNA resulted in a corresponding increase of PEDV infection and an upregulation of cell surface APN expression. Taken together, these data demonstrate that modulation of APN expression by metalloprotease ADAM17 regulates PEDV infection. Hence, the reduction in APN expression represents another component of the anti-PEDV infection response initiated by ADAM17.