Abstract: The critical role of the innate immune system has been confirmed in driving local and systemic inflammation and the cytokine release storm in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This dysregulated immune response is focused on interferon (IFN) and complement activation, which are crucial for the development of metabolic inflammation, local lung tissue damage, and systemic multi-organ failure. IFNs control viral infections by inducing expression of IFN-stimulated genes (ISGs) that restrict distinct steps of viral replication. Therefore, in this review article, we propose the mechanism of SARS-CoV-2-associated acute respiratory disease syndrome, and assess treatment options by considering IFNs and by targeting IFN-antagonist SARS-CoV-2 virulent gene products. Furthermore, we elaborate on the mechanism of the amplified complement-mediated inflammatory cytokine storm, and propose an antiviral and immunotherapeutic strategy against coronavirus disease 2019 (COVID-19).

Keywords: SARS-CoV-2, innate immune system, cytokines, complement, IFNs, virulent


中文翻译：

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IFN 和补体系统的作用：SARS-CoV-2 中的先天免疫


摘要：先天免疫系统在严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 局部和全身炎症以及细胞因子释放风暴中的关键作用已被证实。这种失调的免疫反应主要集中在干扰素 (IFN) 和补体激活上，这对于代谢性炎症、局部肺组织损伤和全身多器官衰竭的发展至关重要。干扰素通过诱导干扰素刺激基因（ISG）的表达来控制病毒感染，这些基因限制了病毒复制的不同步骤。因此，在这篇综述文章中，我们提出了 SARS-CoV-2 相关急性呼吸道疾病综合征的机制，并通过考虑 IFN 和针对 IFN 拮抗剂 SARS-CoV-2 毒力基因产物来评估治疗方案。此外，我们详细阐述了补体介导的炎症细胞因子风暴放大的机制，并提出了针对2019冠状病毒病（COVID-19）的抗病毒和免疫治疗策略。


关键词： SARS-CoV-2、先天免疫系统、细胞因子、补体、干扰素、毒力