短嘴和侏儒症综合征(SBDS)的爆发,由新型鹅细小病毒(NGPV)引起,自2015年以来在中国发生。NGPV,单链DNA病毒,被认为是垂直传播的。然而,NGPV免疫逃避的机制尚不清楚。在这项研究中,我们研究了NGPV感染对鸭胚胎成纤维细胞(DEF)细胞环GMP-AMP合酶(cGAS)-干扰素基因刺激因子(STING)信号通路的影响。我们的发现表明,NGPV感染刺激cGAS的mRNA表达,但导致IFN-β诱导较弱。NGPV阻碍IFN-β和下游干扰素刺激基因的表达,从而减少由干扰素刺激DNA(ISD)和聚(I:C)诱导的IFN-β的分泌。RNA-seq结果显示,NGPV感染下调干扰素mRNA表达,同时增强炎症因子的mRNA表达。此外,病毒蛋白过表达的结果表明,与其它病毒蛋白相比,VP1表现出显著的抑制IFN-β表达的能力。结果表明,只有完整的VP1蛋白能抑制IFN-β的表达,而截短的蛋白VP1U和VP2不具有这样的特征。免疫沉淀实验表明,VP1和VP2均可与IRF7蛋白相互作用,而VP1U没有。总之,我们的发现表明,NGPV感染通过IRF7分子潜在地调节干扰素和干扰素刺激因子的表达和分泌,从而损害宿主的先天免疫应答。受VP1蛋白调控。
Outbreaks of short beak and dwarfism syndrome (SBDS), caused by a novel goose parvovirus (NGPV), have occurred in China since 2015. The NGPV, a single-stranded DNA virus, is thought to be vertically transmitted. However, the mechanism of NGPV immune evasion remains unclear. In this study, we investigated the impact of NGPV infection on the Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway in duck embryonic fibroblast (DEF) cells. Our findings demonstrate that NGPV infection stimulates the mRNA expression of cGAS but results in weak
IFN-β induction. NGPV impedes the expression of
IFN-β and downstream interferon-stimulated genes, thereby reducing the secretion of
IFN-β induced by interferon-stimulating DNA (ISD) and poly (I: C). RNA-seq results show that NGPV infection downregulates interferon mRNA expression while enhancing the mRNA expression of inflammatory factors. Additionally, the results of viral protein over-expression indicate that VP1 exhibits a remarkable ability to inhibit
IFN-β expression compared to other viral proteins. Results indicated that only the intact VP1 protein could inhibit the expression of
IFN-β, while the truncated proteins VP1U and VP2 do not possess such characteristics. The immunoprecipitation experiment showed that both VP1 and VP2 could interact with IRF7 protein, while VP1U does not. In summary, our findings indicate that NGPV infection impairs the host\'s innate immune response by potentially modulating the expression and secretion of interferons and interferon-stimulating factors via IRF7 molecules, which are regulated by the VP1 protein.