SARS-CoV-2 is an emerging coronavirus that causes dysfunctions in multiple human cells and tissues. Studies have looked at the entry of SARS-CoV-2 into host cells mediated by the viral spike protein and human receptor ACE2. However, less is known about the cellular immune responses triggered by SARS-CoV-2 viral proteins. Here, we show that the nucleocapsid of SARS-CoV-2 inhibits host pyroptosis by blocking Gasdermin D (GSDMD) cleavage. SARS-CoV-2-infected monocytes show enhanced cellular interleukin-1β (IL-1β) expression, but reduced IL-1β secretion. While SARS-CoV-2 infection promotes activation of the NLRP3 inflammasome and caspase-1, GSDMD cleavage and pyroptosis are inhibited in infected human monocytes. SARS-CoV-2 nucleocapsid protein associates with GSDMD in cells and inhibits GSDMD cleavage in vitro and in vivo. The nucleocapsid binds the GSDMD linker region and hinders GSDMD processing by caspase-1. These insights into how SARS-CoV-2 antagonizes cellular inflammatory responses may open new avenues for treating COVID-19 in the future.

中文翻译：

---

SARS-CoV-2 核衣壳通过阻断 Gasdermin D 裂解来抑制宿主细胞焦亡

SARS-CoV-2 是一种新兴的冠状病毒，可导致多种人体细胞和组织功能障碍。研究着眼于 SARS-CoV-2 进入由病毒刺突蛋白和人类受体 ACE2 介导的宿主细胞。然而，人们对 SARS-CoV-2 病毒蛋白引发的细胞免疫反应知之甚少。在这里，我们表明 SARS-CoV-2 的核衣壳通过阻断 Gasdermin D (GSDMD) 裂解来抑制宿主细胞焦亡。SARS-CoV-2 感染的单核细胞表现出增强的细胞白细胞介素 1β (IL-1β) 表达，但减少了 IL-1β 分泌。虽然 SARS-CoV-2 感染促进了 NLRP3 炎性体和 caspase-1 的激活，但 GSDMD 裂解和细胞焦亡在受感染的人类单核细胞中受到抑制。SARS-CoV-2 核衣壳蛋白与细胞中的 GSDMD 结合并在体外抑制 GSDMD 切割和体内。核衣壳结合 GSDMD 接头区域并阻碍 caspase-1 处理 GSDMD。这些关于 SARS-CoV-2 如何拮抗细胞炎症反应的见解可能会为未来治疗 COVID-19 开辟新的途径。