Table 1 Differentially Expressed Proteins Identified by iTRAQ Analysis of IPEC-J2 Cells in Response to PDCoV Infection protein name Uniprot accession no. log2 ratios (infection/control) peptides sequence coverage (%) p-values functions Upregulated proteins in PDCoV-infected cells ISG15 ubiqutin-like modifier I3LU39 1.24 18 30.1 3.62 × 10–06 RIG-1/MDA5 mediated induction of IFN-alpha/beta pathways Interferon-stimulated protein 60 F1SCY2 1.09 5 14.6 3.51 × 10–05 Defense response to virus 2′-5′ oligoadenylates synthetase 1, OAS1 F1RJN6 0.81 2 3.1 0.0001 Antiviral protein Radical S-adenosyl methionine domain-containing protein 2 F1S9L2 0.70 6 13.8 1.60 × 10–05 Defense response to virus Interferon induced protein with tetratricopeptide repeats 1, IFIT1 K7GN56 0.70 5 9.6 0.0002 Regulation of defense response to virus Family with sequence similarity 8 member A1 F1RUH9 0.69 1 2.2 0.0103 unknown uncharacterized protein I3LH89 0.658 1 4.7 0.0074 unknown Interferon-induced GTP-binding protein Mx1 K7GKN2 0.58 2 2.0 0.0013 GTPase activity; cellular response to type I interferon Nucleoporin 37 (NUP37) F1SRJ4 0.57 1 5.2 0.0016 Transporting macromolecules Nuclear transcription factor Y submit beta (NFYB) F1SG36 0.55 2 6.3 0.0013 DNA-binding transcription factor activity DNA excision repair protein ERCC-6-like isoform a (ERCC6L) I3LFY4 0.45 1 0.8 0.0496 DNA translocase activity Collagen type IV alpha 1 chain F1RLM1 0.45 1 0.6 0.0153 Component of glomerular basement membranes (GBM) Ribouclease T2 F1SBX8 0.35 2 4.4 0.0004 Ribinuclease T2 activity MRPL32 I3LTC4 0.34 1 11.7 0.0472 translation Phostensin Q767M0 0.32 3 6.8 0.0047 Phosphatase binding Bridging integrator 1 F1RXZ6 0.32 7 22.7 0.0012 Regulation of endocytosis Terpene cyclase/mutase family member I3L7C2 0.29 10 16.7 0.0012 Beta-amyrin synthase activity Secretagogin (SCGN) Q06A97 0.28 2 9.4 0.0214 Calcium binding Interleukin 13 receptor subunit alpha 2 K7GSC6 0.28 2 14.6 0.0370 Obsolete signal transducer activity and cytokine receptor activity FOS-like 1 (FOSL1) F1RU26 0.28 1 6.2 0.0214 DNA-binding transcription factor activity Prolactin regulatory element binding F1SED4 0.27 9 10.1 0.0229 GTPase activator activity CDK-activating kinase assembly factor MAT1 (MNAT1) F6Q8T7 0.27 1 6.4 0.0076 DNA-dependent ATPase activity Intraflagellar transport 81 F1RNN4 0.26 1 3.7 0.0033 Tubulin binding Downregulated proteins in PDCoV-infected cells Very low density lipoprotein receptor (VLDLR) E7CXS1 –0.27 21 22.8 0.0001 Apolipoprotein binding uncharacterized I3LFU8 –0.27 3 5.6 0.0218 unknown Myeloid leukemia factor 2 F1SLT1 –0.28 6 15.8 0.0488 DNA-binding Helicase-like transcription factor (HLTF) I3LM88 –0.28 1 1.9 0.0254 DNA-dependent ATPase activity Ras association domain family member 6 F1RUL8 –0.29 2 5.5 0.0011 Regulation of apoptotic process Nucleoside diphosphate kinase 7 (NME7) F1RPV8 –0.29 3 8.0 0.0279 Synthesis of nucleoside triphosphates Bromodomain adjacent to zinc finger domain 2A (BAZ2A) F1SLA2 –0.29 1 1.2 0.0189 Component of the nucleolar remodeling complex BMP2 inducible kinase I3LT15 –0.29 1 2.8 0.0319 Protein kinase activity RNA helicase (DDX55) F1RFL5 –0.29 1 1.5 0.0274 Catalytic activity TMEM55B F1S8H7 –0.29 1 3.9 0.0445 Catalytic activity Chromatin assembly factor 1 subunit A (CHAF1A) F1S7L7 –0.29 4 5.3 0.0252 Chromo shadow domain binding RNA polymerase II subunit A C-terminal domain phosphatase (CTDP1) F1RWS7 –0.29 2 5.5 0.0123 Promoting the activity of RNA polymerase II uncharacterized I3LIB8 –0.30 2 14.7 0.0373 unknown Intraflagellar transport 172 I3LPC6 –0.30 1 0.69 0.0383 Negative regulation of epithelial cell proliferation Myocyte enhancer factor 2D (MEF2D) F1RP31 –0.30 1 1.9 0.0418 Protein dimerization activity Poly(ADP-ribose) glycohydrolase F1SDW4 –0.31 1 1.3 0.0355 Poly(ADP-ribose) glycohydrolase activity Mitogen-activated protein kinase 4 F1STG5 –0.31 4 4.9 0.0233 Protein serine/threonine kinase activity Anaphase promoting complex subunit 7 (ANAPC7) I3L7Q8 –0.31 4 7.9 0.0218 Ubiquitin protein ligase activity Transmembrane protein 45A F1SKZ6 –0.31 1 3.6 0.0191 Modulates cancer cell chemosensitivity Katanin p60 ATPase-containing subunit A1 I3LVP8 –0.32 2 32.1 0.0181 ATPase activity Ubiquitin associated protein 2 (UBAP2) F1SEA5 –0.32 1 1.7 0.0237 Cadherin binding Ribosomal RNA adenine dimethylase domain containing 1 F1RHJ0 –0.32 1 2.3 0.0391 rRNA (adenine-N6,N6)-dimethyltransferase activity Lemur tyrosine kinase 2 F1RFL2 –0.32 1 1.0 0.0104 Protein serine/threonine kinase activity Poly(ADP-ribose) polymerase family member 10 F1RSK9 –0.32 1 1.8 0.0182 K63-linked polyubiquitin modification-dependent protein binding CDK9 C9E1C9 –0.32 4 11.0 0.0183 Cyclin-dependent protein serine/threonine kinase activity Cystatin C Q0Z8R0 –0.33 2 17.1 0.0282 Cysteine-type endopeptidase inhibitor activity Cyclin and CBS domain divalent metal cation transport mediator 2 F1S849 –0.33 1 1.1 0.0173 Adenylnucleotide binding Protein-serine/threonine kinase F1S069 –0.34 4 8.2 0.0247 Protein serine/threonine kinase activity Aamy domain-containing protein F1S5K2 –0.34 1 2.5 0.0390 Catalytic activity; amino acid transport GATOR complex protein WDR24 I3LF05 –0.34 1 1.4 0.0368 Regulation of autophagy; positive regulation of TOR signaling CD109 antigen isoform 1 preproprotein K7GKY0 –0.35 18 12.9 0.0105 Endopeptidase inhibitor activity Nonspecific serine/threonine protein kinase (AKT2) G9BWQ2 –0.35 7 12.0 0.0310 Transferase activity DNA polymerase delta interacting protein 3 (POLDIP3) F1SJQ4 –0.35 3 3.8 0.0287 RNA binding Exostosin-like glycosyltransferase 2 F1S568 –0.35 1 3.3 0.0215 Transferase activity 4F5 domain-containing protein I3LS25 –0.36 9 42.4 0.0015 Positive regulator of amyloid protein aggregation and proteotoxicity Integrator complex subunit 4 (INTS4) F1STY6 –0.37 3 2.4 0.0429 Involved in the small nuclear RNAs (snRNA) U1 and U2 transcription Smoothelin-like 2 F1RGN8 –0.37 1 2.7 0.0119 Actin cytoskeleton organization Elongation of very long chain fatty acids protein I3L7S8 –0.39 1 21.6 0.0444 Catalytic activity uncharacterized I3LBD1 –0.40 1 7.4 0.0085 unknown Secretory carrier-associated membrane protein F1SJ46 –0.41 7 13.1 0.0144 Protein transport Cadherin 6 F1SP42 –0.42 3 3.7 0.0122 Calcium ion binding Superoxide dismutase I3LUD1 –0.43 2 4.9 0.0139 Superoxide dismutase activity Probable ribosome biogenesis protein C16orf42 homologue (SMARCA2) F1RFZ6 –0.44 1 4.4 0.0470 Involved in ribosome biogenesis Protein zyg-11 homologue B F1S6I1 –0.45 1 3.4 0.0030 Positive regulation of proteasomal ubiquitin-dependent protein catabolic process BCL2 interacting protein 3 I3LDJ9 –0.45 2 6.6 0.0009 Protein homodimerization activity Alpha-(1,6)-fucosyltransferase (FUT8) F1SA54 –0.47 1 3.3 0.0492 Alpha-(1→6)-fucosyltransferase activity Signal peptide peptidase-like 2B F1S8G9 –0.52 2 1.9 0.0190 Protein homodimerization activity INTS3 and NABP interacting protein (INTS4) F1SNA6 –0.54 5 12.5 0.0006 DNA repair Trypsin domain containing 1 F1SUE6 –0.55 1 1.8 0.0215 Serine-type endopeptidase activity UDP-glucose glycoprotein glucosyltransferase 2 F1RP50 –0.62 2 2.3 0.0320 Glycoprotein glucosyltransferase activity Phosphatidylglycerophosphate synthase 1 I3LN95 –0.62 1 2.7 0.0440 Calcium ion binding Metallothionein-2A P79379 –0.63 9 32.8 0.0017 Metal ion binding uncharacterized I3LNY1 –0.66 1 6.5 0.0246 unknown Formin-like 1 I3LH80 –0.83 1 1.8 0.0191 Rho GTPase binding uncharacterized K7GL96 –1.13 1 10.9 0.0412 unknown