Author: Cao, Xiaoling; Tian, Yan; Nguyen, Vi; Zhang, Yuping; Gao, Chao; Yin, Rong; Fan, Daping; Cui, Taixing; Tan, Wenbin
Title: Spike Protein of SARSâ€CoVâ€2 Activates Macrophages and Contributes to Induction of Acute Lung Inflammations in Mice Cord-id: 6n3o0hgb Document date: 2021_5_14
ID: 6n3o0hgb
Snippet: BACKGROUND: Coronavirus disease 2019 (COVIDâ€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 (SARSâ€CoVâ€2) is crucial to mediate viral entry into host cells; however, whether it can be cellularly pathogenic and contribute to pulmonary hyperâ€inflammations in COVIDâ€19 is not well known. METHODS AND FINDINGS: In this study, we developed a Spike proteinâ€pse
Document: BACKGROUND: Coronavirus disease 2019 (COVIDâ€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 (SARSâ€CoVâ€2) is crucial to mediate viral entry into host cells; however, whether it can be cellularly pathogenic and contribute to pulmonary hyperâ€inflammations in COVIDâ€19 is not well known. METHODS AND FINDINGS: In this study, we developed a Spike proteinâ€pseudotyped (Spp) lentivirus with the proper tropism of SARSâ€CoVâ€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 (VSVâ€G) was used as the control. Two hours postâ€infection (hpi), Spp showed more than 27â€75 times more viral burden in the lungs than other organs; it also exhibited about 3â€5 times more viral burden than VSVâ€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 PPARâ€Î³ were quickly upregulated in response to infection of Spp lentivirus in the lungs in vivo as well as in macrophageâ€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 SARSâ€CoVâ€2 alone can induce cellular pathology, e.g. activating macrophages and contributing to induction of acute inflammatory responses.
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