Type I interferons (IFNs) are our first line of defence against a virus. Protein over-expression studies have suggested the ability of SARS-CoV-2 proteins to block IFN responses. Emerging data also suggest that timing and extent of IFN production is associated with manifestation of COVID-19 severity. In spite of progress in understanding how SARS-CoV-2 activates antiviral responses, mechanistic studies into wildtype SARS-CoV-2-mediated induction and inhibition of human type I IFN responses are lacking. Here we demonstrate that SARS-CoV-2 infection induces a mild type I IFN response in vitro and in moderate cases of COVID-19. In vitro stimulation of type I IFN expression and signaling in human airway epithelial cells is associated with activation of canonical transcriptions factors, and SARS-CoV-2 is unable to inhibit exogenous induction of these responses. Our data demonstrate that SARS-CoV-2 is not adept in blocking type I IFN responses and provide support for ongoing IFN clinical trials.

中文翻译：

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SARS-CoV-2感染诱导的I型干扰素应答激活的实验和自然证据

I型干扰素（IFN）是我们抵抗病毒的第一道防线。蛋白质过表达研究表明，SARS-CoV-2蛋白具有阻断IFN反应的能力。新兴数据还表明，IFN产生的时机和程度与COVID-19严重程度的表现有关。尽管在理解SARS-CoV-2如何激活抗病毒应答方面取得了进展，但仍缺乏对野生型SARS-CoV-2介导的诱导和抑制人I型IFN应答的机制研究。在这里，我们证明了SARS-CoV-2感染会在体外和中度COVID-19病例中引起轻度的I型IFN反应。人气道上皮细胞中I型IFN表达和信号转导的体外刺激与规范转录因子的激活有关，SARS-CoV-2无法抑制这些反应的外源诱导。我们的数据表明，SARS-CoV-2不擅长阻断I型IFN反应，并为正在进行的IFN临床试验提供了支持。