Antiviral Activity of Salmonid Gamma Interferon against Infectious

We investigated the antiviral activity and gene induction properties of interferon gamma (IFN-) compared to type I IFN (IFNa1) in Atlantic salmon. IFN- protected salmon cells against infectious pancreatic necrosis virus (IPNV)-induced cytopathic effect (CPE), reduced virus titers, and inhibited the synthesis of the viral structural protein VP3. Moreover, IFN- showed potent antiviral activity against salmonid alphavirus 3 (SAV3) measured as a reduction in virus nsP1 transcripts. IFN- (a type II IFN) had less specific antiviral activity against IPNV than IFNa1, showing a half-maximal effective concentration of 1.6 ng/ml versus 31 pg/ml determined in the CPE reduction assay. Compared to IFNa1, IFN- was a more effective inducer of the antiviral protein GBP, several interferon regulatory transcription factors (IRFs), and the chemokine IP-10. The antiviral activity of IFN- may also in part be ascribed to upregulation of Mx, ISG15, and viperin. These are typical type I IFN-induced genes in mammals and were also more strongly induced by IFNa1 than by IFN- in salmon cells. Fish and mammalian IFN- thus show strikingly similar gene induction properties. Interest-ingly, the antiviral activity of IFN- against IPNV and SAV3 and its ability to induce Mx and ISG15 markedly decreased in the presence of neutralizing antiserum against IFNa1. In contrast, antiIFNa1 had no effect on the induction of IRF-1 and IP-10 by IFN-. This suggests that the antiviral activity of IFN- is partially dependent on IFNa induction. However, because antiIFNa1 could not abolish the IFN--mediated induction of Mx an