Génétique Moléculaire des Virus à ARN Unit, Department of Virology, Institut Pasteur, Université Paris Cité, CNRS UMR3569, 75015 Paris, France.
Viruses. 2022 Jun 8;14(6):1247. doi: 10.3390/v14061247.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic. SARS-CoV-2 is characterized by an important capacity to circumvent the innate immune response. The early interferon (IFN) response is necessary to establish a robust antiviral state. However, this response is weak and delayed in COVID-19 patients, along with massive pro-inflammatory cytokine production. This dysregulated innate immune response contributes to pathogenicity and in some individuals leads to a critical state. Characterizing the interplay between viral factors and host innate immunity is crucial to better understand how to manage the disease. Moreover, the constant emergence of new SARS-CoV-2 variants challenges the efficacy of existing vaccines. Thus, to control this virus and readjust the antiviral therapy currently used to treat COVID-19, studies should constantly be re-evaluated to further decipher the mechanisms leading to SARS-CoV-2 pathogenesis. Regarding the role of the IFN response in SARS-CoV-2 infection, in this review we summarize the mechanisms by which SARS-CoV-2 evades innate immune recognition. More specifically, we explain how this virus inhibits IFN signaling pathways (IFN-I/IFN-III) and controls interferon-stimulated gene (ISG) expression. We also discuss the development and use of IFNs and potential drugs controlling the innate immune response to SARS-CoV-2, helping to clear the infection.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）是当前 COVID-19 大流行的罪魁祸首。SARS-CoV-2 的一个重要特征是能够规避先天免疫反应。早期干扰素（IFN）反应对于建立强大的抗病毒状态是必要的。然而，在 COVID-19 患者中，这种反应较弱且延迟，同时伴有大量促炎细胞因子的产生。这种失调的先天免疫反应导致了发病机制，并在某些个体中导致了危急状态。描述病毒因素与宿主先天免疫之间的相互作用对于更好地了解如何管理该疾病至关重要。此外，新的 SARS-CoV-2 变体不断出现，挑战了现有疫苗的功效。因此，为了控制这种病毒并调整目前用于治疗 COVID-19 的抗病毒疗法，应该不断重新评估研究，以进一步阐明导致 SARS-CoV-2 发病机制的机制。关于 IFN 反应在 SARS-CoV-2 感染中的作用，在这篇综述中，我们总结了 SARS-CoV-2 逃避先天免疫识别的机制。更具体地说，我们解释了这种病毒如何抑制 IFN 信号通路（IFN-I/IFN-III）和控制干扰素刺激基因（ISG）的表达。我们还讨论了 IFNs 的开发和使用以及控制 SARS-CoV-2 先天免疫反应的潜在药物，以帮助清除感染。
