Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing, China.
Front Immunol. 2020 Oct 26;11:545302. doi: 10.3389/fimmu.2020.545302. eCollection 2020.
Viruses typically target host RIG-I-like receptors (RLRs), a group of key factors involved in interferon (IFN) production, to enhance viral infection. To date, though immune evasion methods to contradict IFN production have been characterized for a series of terrestrial viruses, the strategies employed by fish viruses remain unclear. Here, we report that all grass carp reovirus (GCRV) proteins encoded by segments S1 to S11 suppress mitochondrial antiviral signaling protein (MAVS)-mediated IFN expression. First, the GCRV viral proteins blunted the MAVS-induced expression of IFN, and impair MAVS antiviral capacity significantly. Interestingly, subsequent co-immunoprecipitation experiments demonstrated that all GCRV viral proteins interacted with several RLR cascades, especially with TANK-binding kinase 1 (TBK1) which was the downstream factor of MAVS. To further illustrate the mechanisms of these interactions between GCRV viral proteins and host RLRs, two of the viral proteins, NS79 (S4) and VP3 (S3), were selected as representative proteins for two distinguished mechanisms. The obtained data demonstrated that NS79 was phosphorylated by gcTBK1, leading to the reduction of host substrate gcIRF3/7 phosphorylation. On the other hand, VP3 degraded gcMAVS and the degradation was significantly reversed by 3-MA. The biological effects of both NS79 and VP3 were consistently found to be related to the suppression of IFN expression and the promotion of viral evasion. Our findings shed light on the special evasion mechanism utilized by fish virus through IFN regulation, which might differ between fish and mammals.
病毒通常靶向宿主 RIG-I 样受体（RLRs），这是一组参与干扰素（IFN）产生的关键因素，以增强病毒感染。迄今为止，尽管已经描述了一系列陆地病毒逃避 IFN 产生的免疫逃避方法，但鱼类病毒所采用的策略仍不清楚。在这里，我们报告草鱼虹彩病毒（GCRV）编码的 S1 到 S11 节段的所有蛋白均抑制线粒体抗病毒信号蛋白（MAVS）介导的 IFN 表达。首先，GCRV 病毒蛋白减弱了 MAVS 诱导的 IFN 表达，并显著损害了 MAVS 的抗病毒能力。有趣的是，随后的共免疫沉淀实验表明，所有 GCRV 病毒蛋白与几种 RLR 级联反应相互作用，特别是与 MAVS 的下游因子 TANK 结合激酶 1（TBK1）相互作用。为了进一步阐明 GCRV 病毒蛋白与宿主 RLR 之间这些相互作用的机制，选择了两种病毒蛋白，NS79（S4）和 VP3（S3）作为两种不同机制的代表性蛋白。获得的数据表明，NS79 被 gcTBK1 磷酸化，导致宿主底物 gcIRF3/7 磷酸化减少。另一方面，VP3 降解 gcMAVS，而 3-MA 可显著逆转降解。NS79 和 VP3 的生物学效应均与 IFN 表达的抑制和病毒逃避的促进有关。我们的研究结果阐明了鱼类病毒通过 IFN 调节而采用的特殊逃避机制，这可能在鱼类和哺乳动物之间存在差异。
