传染性支气管炎病毒nsp4和nsp15通过调节NF-κB和IRF3信号通路抑制Ⅰ型干扰素表达

Infectious Bronchitis Viruses nsp4 and nsp15 Antagonizes Type Ⅰ Interferon Expression by Regulating the NF-κB and IRF3 Signaling Pathways

为探究传染性支气管炎病毒(IBV)的非结构蛋白在其抑制Ⅰ型干扰素表达作用中的机理,本试验利用IBV流行毒株感染原代鸡胚肾细胞,通过添加poly(I∶C),检测细胞中Ⅰ型干扰素的表达水平,并构建IBV流行毒株各非结构蛋白真核表达载体,转染鸡胚成纤维细胞(DF-1)后转染poly(I∶C),检测细胞中IFN-β、NF-κB以及IRF3的mRNA表达水平。结果显示,IBV JS株能显著抑制由poly(I∶C)诱导的I型干扰素的表达,且nsp3、nsp4、nsp7、nsp14以及nsp15在此过程中发挥重要作用,nsp4和nsp15可通过抑制上游信号通路中的NF-κB或IRF3的表达来抑制IFN-β的转录,拮抗I型干扰素反应。本试验结果可为深入研究IBV的致病机理及其逃避宿主免疫应答的机制提供理论基础。

In order to explore the mechanism of nonstructural proteins(nsp) of infectious bronchitis virus(IBV) in inhibiting the expression of type I interferon, the primary chicken embryo kidney cells were infected with IBV and added with poly(I∶C), and the expression of type Ⅰ interferon were detected. Then the eukaryotic expression vectors of each nonstructural proteins of IBV epidemic strain were constructed and co-transfected into chicken embryo fibroblast(DF-1) with poly(I∶C),then the expression of IFN-β,NF-κB and IRF3 mRNA were analyzed. The results showed that IBV JS strain significantly inhibited the expression of type I interferon induced by poly(I∶C),and nsp3,nsp4,nsp7,nsp14 and nsp15 played an important role in this process. Nsp4 and nsp15 antagonized the transcription of IFN-β by inhibiting the expression of NF-κB or IRF3 in upstream signaling pathways. The results of this study could provide a basis for further study on the pathogenesis of IBV and the mechanism of evading host immune response.