title: Antiviral activity of salmonid gamma interferon against infectious pancreatic necrosis virus and salmonid alphavirus and its dependency on type I interferon.
abstract: We investigated the antiviral activity and gene induction properties of interferon gamma (IFN-γ) compared to type I IFN (IFNa1) in Atlantic salmon. IFN-γ 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-γ showed potent antiviral activity against salmonid alphavirus 3 (SAV3) measured as a reduction in virus nsP1 transcripts. IFN-γ (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-γ 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-γ 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-γ in salmon cells. Fish and mammalian IFN-γ thus show strikingly similar gene induction properties. Interestingly, the antiviral activity of IFN-γ 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-γ. This suggests that the antiviral activity of IFN-γ is partially dependent on IFNa induction. However, because antiIFNa1 could not abolish the IFN-γ-mediated induction of Mx and ISG15 completely, IFN-γ may possibly also induce such genes directly.
authors.affiliation: Norwegian College of Fishery Science, University of Tromsø, 9037 Tromsø, Norway.
authors.forename: Baojian
authors.initials: B
authors.lastname: Sun
authors.forename: Ingrid
authors.initials: I
authors.lastname: Skjæveland
authors.forename: Tina
authors.initials: T
authors.lastname: Svingerud
authors.forename: Jun
authors.initials: J
authors.lastname: Zou
authors.forename: Jorunn
authors.initials: J
authors.lastname: Jørgensen
authors.forename: Børre
authors.initials: B
authors.lastname: Robertsen
mesh_terms: D000524:Alphavirus / Q000187:drug effects; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D020869:Gene Expression Profiling; D018061:Infectious pancreatic necrosis virus / Q000187:drug effects*; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D020317:Salmo salar; D019562:Viral Load / Q000187:drug effects; D014764:Viral Proteins / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D007370:Interferon Type I; D014764:Viral Proteins; D007371:Interferon-gamma