Zhang Jian, Guo Longjun, Yang Lijun, Xu Jiayu, Zhang Lu, Feng Li, Chen Hongyan, Wang Yue
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
Virology. 2018 Apr;517:24-29. doi: 10.1016/j.virol.2018.02.001. Epub 2018 Feb 21.
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.
猪流行性腹泻病毒(PEDV)是猪流行性腹泻(PED)的病原体。PED以急性腹泻、呕吐、脱水为特征,在全球养猪业中造成了严重的经济损失。在此,我们证明,解整合素金属蛋白酶17(ADAM17)的激活导致HEK293和IPEC-J2细胞中PEDV感染减少以及细胞表面氨肽酶N(APN)表达下调,APN是PEDV感染的一个重要进入因子。此外,ADAM17的过表达抑制了HEK293和IPEC-J2细胞中的PEDV感染,而使用ADAM17特异性siRNA消除ADAM17表达导致PEDV感染相应增加以及细胞表面APN表达上调。综上所述,这些数据表明金属蛋白酶ADAM17对APN表达的调节作用调控了PEDV感染。因此,APN表达的降低代表了ADAM17引发的抗PEDV感染反应的另一个组成部分。