The Pirbright Institute, Woking, Surrey, GU24 0NF, United Kingdom.
Sci Rep. 2017 Jun 2;7(1):2719. doi: 10.1038/s41598-017-02951-2.
Interferons (IFNs) are essential components of the host innate immune system and define first-line of defence against pathogens. In mammals, several type I IFNs are identified, however, only limited data is available on the repertoire of IFNs in avian species. Here we report the characterization of chicken IFN-κ (chIFN-κ) near the type I IFN locus on the sex-determining Z chromosome. Genetic, evolutionary and syntenic analyses indicate that chIFN-κ is a type I IFN with conserved genetic features and promoter binding sites. chIFN-κ regulated the IFN-stimulated response element signalling pathways and activated a panel of IFN-regulated genes, antiviral mediators and transcriptional regulators. Priming of chicken primary fibroblasts and tracheal organ cultures with chIFN-κ imparted cellular protections against viral infections both in vitro and ex vivo. To determine whether chIFN-κ defines the antiviral state in developing chicken embryos, we used replication-competent retroviral RCAS vector system to generate transgenic chicken embryos that constitutively and stably expressed chIFN-κ. We could demonstrate that chIFN-κ markedly inhibited the replication of avian RNA viruses in ovo. Collectively, these results shed the light on the repertoire of IFNs in avian species and provide functional data on the interaction of the chIFN-κ with RNA viruses of poultry and public health importance.
干扰素 (IFNs) 是宿主先天免疫系统的重要组成部分,是抵御病原体的第一道防线。在哺乳动物中,已经鉴定出几种类型 I IFN,但关于禽类 IFN 谱的数据非常有限。在这里,我们在性染色体 Z 上的 I 型 IFN 基因座附近报道了鸡 IFN-κ (chIFN-κ) 的特征。遗传、进化和基因图谱分析表明,chIFN-κ 是一种具有保守遗传特征和启动子结合位点的 I 型 IFN。chIFN-κ 调节 IFN 刺激反应元件信号通路,并激活一组 IFN 调节基因、抗病毒介质和转录调节剂。用 chIFN-κ 对鸡原代成纤维细胞和气管器官培养物进行诱导,可在体外和体内赋予细胞对病毒感染的保护。为了确定 chIFN-κ 是否在发育中的鸡胚胎中定义抗病毒状态,我们使用复制型逆转录病毒 RCAS 载体系统生成了稳定表达 chIFN-κ 的转基因鸡胚胎。我们可以证明 chIFN-κ 显著抑制了鸡胚中禽 RNA 病毒的复制。总的来说,这些结果揭示了禽类 IFN 谱,并提供了关于 chIFN-κ 与家禽和公共卫生重要性的 RNA 病毒相互作用的功能数据。