Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia.
Arch Virol. 2023 Jun 13;168(7):178. doi: 10.1007/s00705-023-05792-9.
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with a high mortality rate. The clinical course is attributed to the severity of pneumonia and systemic complications. In COVID-19 patients and murine models of SARS-CoV-2 infection, the disease may be accompanied by excessive production of cytokines, leading to an accumulation of immune cells in affected organs such as lungs. Previous reports have shown that SARS-CoV-2 infection antagonizes interferon (IFN)-dependent antiviral response, thereby preventing the expression of IFN-stimulated genes (ISGs). Lower IFN levels have been linked to more-severe COVID-19. Interleukin 27 (IL27) is a heterodimeric cytokine composed of IL27p28 and EBI3 subunits, which induce both pro- and anti-inflammatory responses. Recently, we and others have reported that IL27 also induces a strong antiviral response in an IFN-independent manner. Here, we investigated transcription levels of both IL27 subunits in COVID-19 patients. The results show that SARS-CoV-2 infection modulates TLR1/2-MyD88 signaling in PBMCs and monocytes and induces NF-κB activation and expression of NF-κB-target genes that are dependent on a robust pro-inflammatory response, including EBI3; and activates IRF1 signaling which induces IL27p28 mRNA expression. The results suggest that IL27 induces a robust STAT1-dependent pro-inflammatory and antiviral response in an IFN-independent manner in COVID-derived PBMCs and monocytes as a function of a severe clinical course of COVID-19. Similar results were observed in macrophages stimulated with the SARS-CoV-2 spike protein. Thus, IL27 can trigger an antiviral response in the host, suggesting the possibility of novel therapeutics against SARS-CoV-2 infection in humans.
新型冠状病毒病（COVID-19）是由严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染引起的，其死亡率很高。其临床过程归因于肺炎和全身并发症的严重程度。在 COVID-19 患者和 SARS-CoV-2 感染的鼠模型中，疾病可能伴随着细胞因子的过度产生，导致免疫细胞在受影响的器官（如肺部）中积聚。先前的报告表明，SARS-CoV-2 感染拮抗干扰素（IFN）依赖性抗病毒反应，从而阻止 IFN 刺激基因（ISGs）的表达。较低的 IFN 水平与更严重的 COVID-19 相关。白细胞介素 27（IL27）是一种异二聚体细胞因子，由 IL27p28 和 EBI3 亚基组成，可诱导促炎和抗炎反应。最近，我们和其他人报告称，IL27 还以 IFN 非依赖性方式诱导强烈的抗病毒反应。在这里，我们研究了 COVID-19 患者中两种 IL27 亚基的转录水平。结果表明，SARS-CoV-2 感染调节 PBMCs 和单核细胞中的 TLR1/2-MyD88 信号，并诱导 NF-κB 激活和 NF-κB 靶基因的表达，这些基因依赖于强烈的促炎反应，包括 EBI3；并激活 IRF1 信号，诱导 IL27p28 mRNA 表达。结果表明，IL27 以 IFN 非依赖性方式诱导 COVID 衍生的 PBMCs 和单核细胞中强大的 STAT1 依赖性促炎和抗病毒反应，作为 COVID-19 严重临床过程的功能。用 SARS-CoV-2 刺突蛋白刺激巨噬细胞时观察到类似的结果。因此，IL27 可以在宿主中引发抗病毒反应，这表明针对人类 SARS-CoV-2 感染的新型治疗方法的可能性。
