Background: Coronavirus disease 2019 (COVID-19) patients exhibit multiple organ malfunctions with a primary manifestation of acute and diffuse lung injuries. The Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial to mediate viral entry into host cells; however, whether it can be cellularly pathogenic and contribute to pulmonary hyper-inflammations in COVID-19 is not well known. Methods and Findings: In this study, we developed a Spike protein-pseudotyped (Spp) lentivirus with the proper tropism of SARS-CoV-2 Spike protein on the surface and tracked down the fate of Spp in wild type C57BL/6J mice receiving intravenous injection of the virus. A lentivirus with vesicular stomatitis virus glycoprotein (VSV-G) was used as the control. Two hours post-infection (hpi), Spp showed more than 27-75 times more viral burden in the lungs than other organs; it also exhibited about 3-5 times more viral burden than VSV-G lentivirus in the lungs, liver, kidney and spleen. Acute pneumonia was evident in animals 24 hpi. Spp lentivirus was mainly found in LDLR+ macrophages and pneumocytes in the lungs, but not in MARC1+ macrophages. IL6, IL10, CD80 and PPAR-γ were quickly upregulated in response to infection of Spp lentivirus in the lungs in vivo as well as in macrophage-like RAW264.7 cells in vitro. We further confirmed that forced expression of the Spike protein in RAW264.7 cells could significantly increase the mRNA levels of the same panel of inflammatory factors. Conclusions: Our results demonstrate that the Spike protein of SARS-CoV-2 alone can induce cellular pathology, e.g. activating macrophages and contributing to induction of acute inflammatory responses.

中文翻译：

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SARS-CoV-2 的刺突蛋白激活巨噬细胞并有助于诱导小鼠急性肺部炎症

背景：2019 年冠状病毒病 (COVID-19) 患者表现出多器官功能障碍，主要表现为急性和弥漫性肺损伤。严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 的 Spike 蛋白对于介导病毒进入宿主细胞至关重要；然而，它是否可以在细胞上致病并导致 COVID-19 的肺部过度炎症尚不清楚。方法和发现：在这项研究中，我们开发了一种 Spike 蛋白假型 (Spp) 慢病毒，其表面具有 SARS-CoV-2 Spike 蛋白的适当嗜性，并追踪了 Spp 在接受静脉注射的野生型 C57BL/6J 小鼠中的命运注射病毒。具有水泡性口炎病毒糖蛋白（VSV-G）的慢病毒用作对照。感染后两小时 (hpi)，Spp 在肺部的病毒负荷是其他器官的 27-75 倍以上；它还在肺、肝、肾和脾中表现出比 VSV-G 慢病毒高约 3-5 倍的病毒负荷。动物感染后 24 小时明显出现急性肺炎。慢病毒主要存在于肺中的 LDLR+ 巨噬细胞和肺细胞中，但不在 MARC1+ 巨噬细胞中。IL6、IL10、CD80 和 PPAR-γ 响应体内肺中 Spp 慢病毒的感染以及体外巨噬细胞样 RAW264.7 细胞中的快速上调。我们进一步证实，在 RAW264.7 细胞中强制表达 Spike 蛋白可以显着增加同一组炎症因子的 mRNA 水平。结论：我们的结果表明，单独的 SARS-CoV-2 的 Spike 蛋白可以诱导细胞病理学，例如