Department of Swine Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.
Institute of Animal Husbandry and Veterinary, Shanghai Academy of Agricultural Science, Shanghai, China.
Front Immunol. 2022 Jul 25;13:984448. doi: 10.3389/fimmu.2022.984448. eCollection 2022.
Interferons (IFNs) including type I/III IFNs are the major components of the host innate immune response against porcine epidemic diarrhea virus (PEDV) infection, and several viral proteins have been identified to antagonize type I/III IFNs productions through diverse strategies. However, the modulation of PEDV infection upon the activation of the host's innate immune response has not been fully characterized. In this study, we observed that various IFN-stimulated genes (ISGs) were upregulated significantly in a time- and dose-dependent manner in LLC-PK1 cells infected with the PEDV G2 strain FJzz1. The transcriptions of IRF9 and STAT1 were increased markedly in the late stage of FJzz1 infection and the promotion of the phosphorylation and nuclear translocation of STAT1, implicating the activation of the JAK-STAT signaling pathway during FJzz1 infection. In addition, abundant type I/III IFNs were produced after FJzz1 infection. However, type I/III IFNs and ISGs decreased greatly in FJzz1-infected LLC-PK1 cells following the silencing of the RIG-I-like receptors (RLRs), including RIG-I and MDA5, and the Toll-like receptors (TLRs) adaptors, MyD88 and TRIF. Altogether, FJzz1 infection induces the production of type-I/III IFNs in LLC-PK1 cells, in which RLRs and TLRs signaling pathways are involved, followed by the activation of the JAK-STAT signaling cascade, triggering the production of numerous ISGs to exert antiviral effects of innate immunity.
干扰素 (IFNs) 包括 I 型/III 型 IFNs 是宿主固有免疫反应抵抗猪流行性腹泻病毒 (PEDV) 感染的主要组成部分，几种病毒蛋白已被鉴定出通过多种策略拮抗 I 型/III 型 IFNs 的产生。然而，宿主固有免疫反应激活后对 PEDV 感染的调节尚未完全阐明。在本研究中，我们观察到在 LLC-PK1 细胞中感染 PEDV G2 株 FJzz1 时，各种 IFN 刺激基因 (ISGs) 以时间和剂量依赖的方式显著上调。FJzz1 感染后期，IRF9 和 STAT1 的转录明显增加，STAT1 的磷酸化和核转位促进，表明 JAK-STAT 信号通路在 FJzz1 感染过程中被激活。此外，FJzz1 感染后产生大量 I 型/III 型 IFNs。然而，在沉默 RIG-I 样受体 (RLRs)（包括 RIG-I 和 MDA5）和 Toll 样受体 (TLRs) 衔接子 MyD88 和 TRIF 后，FJzz1 感染的 LLC-PK1 细胞中 I 型/III 型 IFNs 和 ISGs 大量减少。总之，FJzz1 感染诱导 LLC-PK1 细胞产生 I 型/III 型 IFNs，其中涉及 RLRs 和 TLRs 信号通路，随后 JAK-STAT 信号级联被激活，触发大量 ISGs 的产生，发挥固有免疫的抗病毒作用。
