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Spike Protein of SARS-CoV-2 Activates Macrophages and Contributes to Induction of Acute Lung Inflammations in Mice

Xiaoling Cao, Yan Tian, Vi Nguyen, Yuping Zhang, Chao Gao, Rong Yin, Wayne Carver, Daping Fan, Helmut Albrecht, Taixing Cui, View ORCID ProfileWenbin Tan
doi: https://doi.org/10.1101/2020.12.07.414706
Xiaoling Cao
1Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina, USA
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Yan Tian
1Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina, USA
2Department of Obstetrics and Gynecology, Xiangya Hospital, Central South University, Changsha, Hunan, China
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Vi Nguyen
1Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina, USA
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Yuping Zhang
1Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina, USA
3Department of General Surgery, The 3rd Xiangya Hospital of Central South University, Changsha, Hunan, China
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Chao Gao
1Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina, USA
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Rong Yin
1Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina, USA
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Wayne Carver
1Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina, USA
6Biomedical Engineering Program, College of Engineering and Computing University of South Carolina, Columbia, South Carolina, USA
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Daping Fan
1Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina, USA
6Biomedical Engineering Program, College of Engineering and Computing University of South Carolina, Columbia, South Carolina, USA
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Helmut Albrecht
4Department of Internal Medicine, Prisma Health Medical Group, Columbia, Columbia, South Carolina, USA
5Department of Internal Medicine, School of Medicine, University of South Carolina, Columbia, South Carolina, USA
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Taixing Cui
1Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina, USA
6Biomedical Engineering Program, College of Engineering and Computing University of South Carolina, Columbia, South Carolina, USA
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Wenbin Tan
1Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina, USA
6Biomedical Engineering Program, College of Engineering and Computing University of South Carolina, Columbia, South Carolina, USA
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  • ORCID record for Wenbin Tan
  • For correspondence: wenbin.tan@uscmed.sc.edu
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Abstract

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 Statement

The authors have declared no competing interest.

Footnotes

  • Conflict of Interest: Disclosure: None Declared

  • Disclaimer Any views expressed here represent personal opinion and do not necessarily reflect those of the U.S. Department of Health and Human Services or the United States federal government.

  • Prior Publication: None of the material in this manuscript has been published or is under consideration for publication elsewhere, including the Internet.

  • Funding statement: This work was supported by grants from the National Institutes of Health (AR073172 to W.T., HL131667 to T.C.) and the Department of Defense/CDMRP (W81XWH1810096 to WT).

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted December 07, 2020.
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Spike Protein of SARS-CoV-2 Activates Macrophages and Contributes to Induction of Acute Lung Inflammations in Mice
Xiaoling Cao, Yan Tian, Vi Nguyen, Yuping Zhang, Chao Gao, Rong Yin, Wayne Carver, Daping Fan, Helmut Albrecht, Taixing Cui, Wenbin Tan
bioRxiv 2020.12.07.414706; doi: https://doi.org/10.1101/2020.12.07.414706
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Spike Protein of SARS-CoV-2 Activates Macrophages and Contributes to Induction of Acute Lung Inflammations in Mice
Xiaoling Cao, Yan Tian, Vi Nguyen, Yuping Zhang, Chao Gao, Rong Yin, Wayne Carver, Daping Fan, Helmut Albrecht, Taixing Cui, Wenbin Tan
bioRxiv 2020.12.07.414706; doi: https://doi.org/10.1101/2020.12.07.414706

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