Qian Wei, Wei Xiaoqin, Li Yongtao, Guo Kelei, Zou Zhong, Zhou Hongbo, Jin Meilin
State Key Laboratory of Agricultural Microbiology and College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
State Key Laboratory of Agricultural Microbiology and College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China; College of Agricultural and Animal Husbandry, Tibet University, Linzhi, China.
Dev Comp Immunol. 2018 Jan;78:1-13. doi: 10.1016/j.dci.2017.09.004. Epub 2017 Sep 8.
In mammals, IFN regulatory factor (IRF) 1 can activates cellular genes and promotes viral resistance against some DNA and RNA viruses. Most IRFs have been identified as critical regulators in the IFN responses in both mammals and fish. In ducks, however, the functional role of IRF1 remains unknown. Here, we identified duck IRF1 (duIRF1) is essential to counteract viral invasion. duIRF1 is most abundant in duck spleen, and virus infection or poly(I:C) stimulation significantly induced duIRF1 expression in vivo and in vitro. Overexpression of duRF1 induces the expression of type I IFN-β, type III IFN-λ, and interferon stimulated genes (ISGs) in duck embryo fibroblasts (DEFs), initiating cells resistant to avian viruses infection. More importantly, we found duIRF1 interacts with duck myeloid differentiation factor 88 (duMyD88) to activate duck IFN-β, different from IRF3 and IRF7, which involve in IFN expression through the retinoic acid-inducible gene I (RIG-I)-like receptor pathway in mammals. Together, these results indicate that duIRF1 effectively inhibits viral replication through the induction of IFN and antiviral ISGs. This will help with understanding the role of duIRF1 mediated antiviral responses by innate immune mechanisms.
在哺乳动物中,干扰素调节因子(IRF)1可激活细胞基因,并增强对某些DNA和RNA病毒的抗病毒能力。大多数IRF已被确定为哺乳动物和鱼类中干扰素反应的关键调节因子。然而,在鸭中,IRF1的功能作用尚不清楚。在此,我们鉴定出鸭IRF1(duIRF1)对于抵抗病毒入侵至关重要。duIRF1在鸭脾脏中含量最为丰富,病毒感染或聚肌苷酸-聚胞苷酸(poly(I:C))刺激可在体内和体外显著诱导duIRF1表达。duRF1的过表达可诱导鸭胚成纤维细胞(DEFs)中I型干扰素-β、III型干扰素-λ和干扰素刺激基因(ISGs)的表达,使细胞对禽流感病毒感染产生抗性。更重要的是,我们发现duIRF1与鸭髓样分化因子88(duMyD88)相互作用以激活鸭干扰素-β,这与IRF3和IRF7不同,后者在哺乳动物中通过视黄酸诱导基因I(RIG-I)样受体途径参与干扰素表达。总之,这些结果表明duIRF1通过诱导干扰素和抗病毒ISGs有效抑制病毒复制。这将有助于理解duIRF1通过先天免疫机制介导抗病毒反应的作用。