PT  - JOURNAL ARTICLE
AU  - Xiaoling Cao
AU  - Yan Tian
AU  - Vi Nguyen
AU  - Yuping Zhang
AU  - Chao Gao
AU  - Rong Yin
AU  - Wayne Carver
AU  - Daping Fan
AU  - Helmut Albrecht
AU  - Taixing Cui
AU  - Wenbin Tan
TI  - Spike Protein of SARS-CoV-2 Activates Macrophages and Contributes to Induction of Acute Lung Inflammations in Mice
AID  - 10.1101/2020.12.07.414706
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.12.07.414706
4099  - http://biorxiv.org/content/early/2020/12/07/2020.12.07.414706.short
4100  - http://biorxiv.org/content/early/2020/12/07/2020.12.07.414706.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.