Zhaoqing Branch Center of Guangdong Laboratory for Lingnan Modern Agricultural Science and Technology, Zhaoqing, 526000, Guangdong Province, People's Republic of China; Guangdong Province Key Laboratory Microbial Signals & Disease Control, and Integrative Microbiology Research Centre, South China Agricultural University, Guangzhou, 510642, Guangdong Province, People's Republic of China.
Zhaoqing Institute of Biotechnology Co., Ltd., Zhaoqing, 526238, Guangdong Province, People's Republic of China.
Virology. 2023 May;582:114-127. doi: 10.1016/j.virol.2023.03.017. Epub 2023 Apr 5.
Coronavirus infection induces a variety of cellular antiviral responses either dependent on or independent of type I interferons (IFNs). Our previous studies using Affymetrix microarray and transcriptomic analysis revealed the differential induction of three IFN-stimulated genes (ISGs), IRF1, ISG15 and ISG20, by gammacoronavirus infectious bronchitis virus (IBV) infection of IFN-deficient Vero cells and IFN-competent, p53-defcient H1299 cells, respectively. In this report, the induction kinetics and anti-IBV functions of these ISGs as well as mechanisms underlying their differential induction are characterized. The results confirmed that these three ISGs were indeed differentially induced in H1299 and Vero cells infected with IBV, significantly more upregulation of IRF1, ISG15 and ISG20 was elicited in IBV-infected Vero cells than that in H1299 cells. Induction of these ISGs was also detected in cells infected with human coronavirus-OC43 (HCoV-OC43) and porcine epidemic diarrhea virus (PEDV), respectively. Manipulation of their expression by overexpression, knockdown and/or knockout demonstrated that IRF1 played an active role in suppressing IBV replication, mainly through the activation of the IFN pathway. However, a minor, if any, role in inhibiting IBV replication was played by ISG15 and ISG20. Furthermore, p53, but not IRF1, was implicated in regulating the IBV infection-induced upregulation of ISG15 and ISG20. This study provides new information on the mechanisms underlying the induction of these ISGs and their contributions to the host cell antiviral response during IBV infection.
冠状病毒感染诱导多种依赖或不依赖 I 型干扰素 (IFN) 的细胞抗病毒反应。我们之前的研究使用 Affymetrix 微阵列和转录组分析发现，γ冠状病毒传染性支气管炎病毒 (IBV) 感染 IFN 缺陷的 Vero 细胞和 IFN 敏感、p53 缺陷的 H1299 细胞时，分别诱导三种 IFN 刺激基因 (ISG)，IRF1、ISG15 和 ISG20 的差异诱导。在本报告中，我们对这些 ISG 的诱导动力学和抗 IBV 功能以及其差异诱导的机制进行了描述。结果证实，这三种 ISG 在感染 IBV 的 H1299 和 Vero 细胞中确实存在差异诱导，IBV 感染的 Vero 细胞中 IRF1、ISG15 和 ISG20 的上调更为明显。在感染人冠状病毒-OC43 (HCoV-OC43) 和猪流行性腹泻病毒 (PEDV) 的细胞中也检测到这些 ISG 的诱导。通过过表达、敲低和/或敲除对它们的表达进行操纵表明，IRF1 在抑制 IBV 复制中发挥积极作用，主要通过激活 IFN 途径。然而，ISG15 和 ISG20 在抑制 IBV 复制中仅发挥次要作用。此外，p53 而非 IRF1 参与调节 IBV 感染诱导的 ISG15 和 ISG20 的上调。本研究为这些 ISG 的诱导机制及其在 IBV 感染期间宿主细胞抗病毒反应中的作用提供了新信息。
