Laboratory of Animal Infectious Diseases and Molecular Immunology, College of Animal Science and Technology, Guangxi University, Nanning, China.
Guangxi Zhuang Autonomous Region Engineering Research Center of Veterinary Biologics, Nanning, China.
Microbiol Spectr. 2023 Jun 15;11(3):e0070123. doi: 10.1128/spectrum.00701-23. Epub 2023 May 4.
The interferon (IFN) system is an extremely powerful antiviral response in animal cells. The subsequent effects caused by porcine astrovirus type 1 (PAstV1) IFN activation are important for the host's response to viral infections. Here, we show that this virus, which causes mild diarrhea, growth retardation, and damage of the villi of the small intestinal mucosa in piglets, induces an IFN response upon infection of PK-15 cells. Although IFN-β mRNA was detected within infected cells, this response usually occurs during the middle stages of infection, after genome replication has taken place. Treatment of PAstV1-infected cells with the interferon regulatory factor 3 (IRF3) inhibitor BX795 decreased IFN-β expression, whereas the nuclear factor kappa light chain enhancer of activated B cells (NF-κB) inhibitor BAY11-7082 did not. These findings indicate that PAstV induced the production of IFN-β via IRF3-mediated rather than NF-κB-mediated signaling pathways in PK-15 cells. Moreover, PAstV1 increased the protein expression levels of retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5) in PK-15 cells. The knockdown of RIG-I and MDA5 decreased the expression levels of IFN-β and the viral loads and increased the infectivity of PAstV1. In conclusion, PAstV1 induced the production of IFN-β via the RIG-I and MDA5 signaling pathways, and the IFN-β produced during PAstV1 infection inhibited viral replication. These results will help provide new evidence that PAstV1-induced IFNs may protect against PAstV replication and pathogenesis. Astroviruses (AstVs) are widespread and can infect multiple species. Porcine astroviruses produce mainly gastroenteritis and neurological diseases in pigs. However, astrovirus-host interactions are less well studied, particularly with respect to their antagonism of IFN. Here, we report that PAstV1 acts via IRF3 transcription pathway activation of IFN-β. In addition, the knockdown of RIG-I and MDA5 attenuated the production of IFN-β induced by PAstV1 in PK-15 cells and increased efficient viral replication . We believe that these findings will help us to better understand the mechanism of how AstVs affect the host IFN response.
干扰素 (IFN) 系统是动物细胞中一种极其强大的抗病毒反应。猪星状病毒 1 型 (PAstV1) IFN 激活引起的后续效应对于宿主对病毒感染的反应很重要。在这里，我们表明，这种病毒会导致仔猪轻度腹泻、生长迟缓以及小肠黏膜绒毛损伤，在感染 PK-15 细胞时会引发 IFN 反应。虽然在感染细胞中检测到 IFN-β mRNA，但这种反应通常发生在感染的中期，即在基因组复制之后。用干扰素调节因子 3 (IRF3) 抑制剂 BX795 处理 PAstV1 感染的细胞会降低 IFN-β 的表达，而核因子 κB 轻链增强子的激活 B 细胞 (NF-κB) 抑制剂 BAY11-7082 则不会。这些发现表明，PAstV 通过 PK-15 细胞中 IRF3 介导而不是 NF-κB 介导的信号通路诱导 IFN-β 的产生。此外，PAstV1 增加了 PK-15 细胞中视黄酸诱导基因 I (RIG-I) 和黑色素瘤分化相关蛋白 5 (MDA5) 的蛋白表达水平。RIG-I 和 MDA5 的敲低降低了 IFN-β 的表达水平和病毒载量，并增加了 PAstV1 的感染性。总之，PAstV1 通过 RIG-I 和 MDA5 信号通路诱导 IFN-β 的产生，而 PAstV1 感染期间产生的 IFN-β 抑制了病毒复制。这些结果将有助于提供新的证据，表明 PAstV1 诱导的 IFNs 可能有助于防止 PAstV 复制和发病机制。星状病毒 (AstVs) 广泛存在，可感染多种物种。猪星状病毒主要在猪中引起胃肠炎和神经系统疾病。然而，星状病毒与宿主的相互作用研究较少，特别是关于它们对抗 IFN 的作用。在这里，我们报告 PAstV1 通过 IFN-β 的 IRF3 转录途径激活来发挥作用。此外，PK-15 细胞中 RIG-I 和 MDA5 的敲低减弱了 PAstV1 诱导的 IFN-β 的产生，并增加了有效的病毒复制。我们相信这些发现将帮助我们更好地理解 AstVs 如何影响宿主 IFN 反应的机制。
