Norwegian College of Fishery Science, University of Tromsø, 9037 Tromsø, Norway.
J Virol. 2011 Sep;85(17):9188-98. doi: 10.1128/JVI.00319-11. Epub 2011 Jun 22.
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.
我们研究了干扰素γ（IFN-γ）与 I 型干扰素（IFNa1）相比在大西洋鲑鱼中的抗病毒活性和基因诱导特性。IFN-γ 可保护鲑鱼细胞免受传染性胰腺坏死病毒（IPNV）诱导的细胞病变效应（CPE），降低病毒滴度，并抑制病毒结构蛋白 VP3 的合成。此外，IFN-γ 对鲑鱼甲肝病毒 3（SAV3）表现出有效的抗病毒活性，表现在病毒 nsP1 转录物减少。IFN-γ（II 型 IFN）对 IPNV 的抗病毒活性不如 IFNa1 特异性，在 CPE 减少测定中，其半最大有效浓度为 1.6ng/ml，而 IFNa1 为 31pg/ml。与 IFNa1 相比，IFN-γ 是抗病毒蛋白 GBP、几种干扰素调节转录因子（IRFs）和趋化因子 IP-10 的更有效的诱导剂。IFN-γ 的抗病毒活性部分归因于 Mx、ISG15 和 viperin 的上调。这些是哺乳动物中典型的 I 型 IFN 诱导基因，在鲑鱼细胞中也比 IFNa1 更强烈地被诱导。因此，鱼类和哺乳动物 IFN-γ 显示出惊人相似的基因诱导特性。有趣的是，在存在针对 IFNa1 的中和抗血清的情况下，IFN-γ 对 IPNV 和 SAV3 的抗病毒活性及其诱导 Mx 和 ISG15 的能力明显降低。相比之下，抗 IFNa1 对 IFN-γ 诱导 IRF-1 和 IP-10 没有影响。这表明 IFN-γ 的抗病毒活性部分依赖于 IFNa 诱导。然而，由于抗 IFNa1 不能完全消除 IFN-γ 介导的 Mx 和 ISG15 的诱导，IFN-γ 可能也可以直接诱导这些基因。
