Voltage-dependent anion channels (VDACs) located in the mitochondrial outer membrane are mitochondrial porins that play central roles in regulating cell life and death. In this present report, the VDAC protein 1 from grass carpCtenopharyngodon idella(designated asCiVDAC1) was found to be upregulated by grass carp reovirus (GCRV) infection through two-dimensional gel electrophoresis and protein analysis of infectedC. idellakidney (CIK) cells. The full-length cDNA ofCiVDAC1was 995 bp with an open reading frame (ORF) of 852 bp that encodes a putative 283-amino acid protein. Phylogenic analysis revealed that the complete ORF of CiVDAC1 demonstrated high identity with well characterized mammalian homologs. The deducedCiVDAC1protein contains ana-helix at the amino terminal, 19 membrane-spanningb-strands, and one eukaryotic mitochondrial porin signature motif. Tissue tropism analysis indicated thatCiVDAC1is abundant in muscle, heart, skin, swim bladder, trunk kidney and spleen. Transcriptional expression profiles indicated that the CiVDAC1gene was upregulated upon viral challenge in a manner similar to theMx2gene, which is a marker gene used to indicate activation of innate antiviral immunity. Similar expression patterns of the CiVDAC1gene were observed in CIK cells stimulated with poly (I:C), as well as grass carp kidney tissue challenged with GCRVin vivo. CiVDAC1 silencing in CIK cells had no impact on progeny virus production, but over-expression ofCiVDAC1 in vivo showed strongly protect against challenge with live virus. To interpret the role of other VDAC proteins in viral pathogenesis,CiVDAC2was characterized and showed to respond positively to GCRV challenge, which suggested thatCiVDAC2might functionally complementCiVDAC1inC. idella. The present data did demonstrate thatCiVDAC1might be mediated grass carp antiviral immune response Shen X, Wang T, Xu D, et al. Proteomic identification, characterization and expression analysis of Ctenopharyngodon idella VDAC1 upregulated by grass carp reovirus infection[J]. Fish & shellfish immunology, 2014.