The porcine epidemic diarrhea virus (PEDV) is an enveloped, single-stranded positive-sense RNA virus that causes porcine epidemic diarrhea (PED), an acute and highly contagious enteric disease in pigs.PED is characterized by severe diarrhea, vomiting, dehydration, and a mortality rate of up to 90% in suckling piglets.PED was first reported in Belgium and the United Kingdom in 1978, and frequent outbreaks have occurred in various Asian countries.Since 2007, acute PED outbreaks have continually occurred in Thailand, China, and the USA,which have resulted in substantial economic losses.The continued outbreaks of PED, despite control efforts, have caused widespread concern.Proteomics techniques are effective tools for characterizing protein expression profiles,and have been used widely to investigate disease-associated proteins.Among current proteomics methods,quantitative high-throughput proteomics approaches are useful for the analysis of infection-associated proteins of pathogens.In our current study, we used a quantitative proteomics approach based on an iTRAQ tandem mass spectrometry (MS/MS) technique to identify proteins differentially expressed between PEDV-infected and mock-infected Vero E6 cells.We analyzed the differential protein profile of PEDV-infected Vero E6 cells using mass spectrometry and an isobaric tag for relative and absolute quantification.A total of 126 proteins were identified that were differentially expressed between the PEDV-infected and mock-infected groups (P<0.05, quantitative ratio ≥ 1.2), among which the expression of 58 proteins was up-regulated and that of 68 proteins was down-regulated in the PEDV-infected Vero E6 cells, involving in integrin β2/β3, cystatin-C.The Gene Ontology analysis indicated that the molecular function of the differentially expressed proteins (DEPs) was primarily related to binding and catalytic activity, and that the biological functions in which the DEPs are involved included metabolism, organismal systems, cellular processes, genetic information processing, environmental information processing, and diseases.Among the disease-related functions, certain anti-viral pathways and proteins, such as the RIG-I-like receptor,Rap1, autophagy, mitogen-activated protein kinase, PI3K-Akt and Jak-STAT signaling pathways, and integrin β2/β3 and cystatin-C proteins, represented potential factors in PEDV infection.To the best of our knowledge, our study represents the analysis of the interactions between PEDV and Vero E6 cells using a quantitative proteomics technique.PEDV infection-associated pathways and proteins are described and discussed based on the bioinformatics analysis of the differentially expressed proteins.Our analysis of Vero E6 cell responses to PEDV infection identified relevant targets for subsequent in-depth studies of PEDV pathogenesis, expand the current knowledge base regarding the interaction between the PEDV and the host cell, and provide useful basic information about other coronaviruses.Although the Vero E6 cells are highly susceptible to PEDV infection and facilitate experimental design and performance for proteomics, the Vero E6 cell line is an interferon-deficient cell line and not a pig cell line.So, the detailed functions of these pathways and proteins in PEDV infection require further verification in the actual host cells of PEDV.