Activation of cytokine expression occurs through the TNFα/NF-κB-mediated pathway in birnavirus-infected cells

The infectious pancreatic necrosis virus (IPNV) belongs to the Birnaviridae family of viruses and causes acute contagious diseases in a number of economically important freshwater and marine fish. In this study, we infected zebrafish embryonic cells (ZF4) with IPNV and analyzed the gene expression patterns of normal and infected cells using quantitative real-time PCR. We identified a number of immune response genes, including ifna, ifng, mx, irf1, irf2, irf4, tnfa, tnjb, il-15, il-26, ccI4 and mmp family genes, that are induced after viral infection. Transcriptional regulators, including cebpb, junb, nfkb and stat1, stat4 and stat5, were also upregulated in IPNV-infected cells. In addition, we used Pathway Studio software to identify TNF alpha as having the greatest downstream influence among these altered genes. Treating virus-infected cells with an siRNA targeting TNFa inhibited NF-kappa B expression. To further interrupt the TNF alpha/NF-kappa B-mediated pathway, the expression levels of cytokines and metalloproteinases were inhibited in IPNV-infected cells. These data suggest that, during IPNV infection, the expression of cytokines and metalloproteinases might be initiated through the TNF alpha/NF-kappa B-mediated pathway. The modulation of TNF alpha/NF-kappa B-related mechanisms may provide a therapeutic strategy for inhibiting viral infection in teleosts. (C) 2011 Elsevier Ltd. All rights reserved.