Tyrkalska, Sylwia D. 
ORCID: 0000-0001-6654-0163, Martinez-Lopez, Alicia, Arroyo, Ana B., Martinez-Morcillo, Francisco J., Candel, Sergio, Garcia-Moreno, Diana, Mesa-Del-Castillo, Pablo, Cayuela, Maria L. and Mulero, Victoriano ORCID: 0000-0001-9527-0211
(2022).
Differential proinflammatory activities of Spike proteins of SARS-CoV-2 variants of concern.
Sci. Adv., 8 (37).
WASHINGTON:
AMER ASSOC ADVANCEMENT SCIENCE.
ISSN 2375-2548
Abstract
The coronavirus disease 2019 (COVID-19) pandemic turned the whole world upside down in a short time. One of the main challenges faced has been to understand COVID-19-associated life-threatening hyperinflammation, the so-called cytokine storm syndrome (CSS). We report here the proinflammatory role of Spike (S) proteins from different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern in zebrafish. We found that wild-type/Wuhan variant 51 (S1WT) promoted neutrophil and macrophage recruitment, local and systemic hyperinflammation, emergency myelopoiesis, and hemorrhages. In addition, S1 gamma was more proinflammatory while S1 delta was less proinflammatory than S1WT, and, notably, S1 beta promoted delayed and long-lasting inflammation. Pharmacological inhibition of the canonical inflammasome alleviated S1-induced inflammation and emergency myelopoiesis. In contrast, genetic inhibition of angiotensin-converting enzyme 2 strengthened the proinflammatory activity of S1, and angiotensin (1-7) fully rescued S1-induced hyperinflammation and hemorrhages. These results shed light into the mechanisms orchestrating the COVID-19-associated CSS and the host immune response to different SARS-CoV-2 S protein variants.
| Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||
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| URN: | urn:nbn:de:hbz:38-683367 | ||||||||||||||||||||||||||||||||||||||||
| DOI: | 10.1126/sciadv.abo0732 | ||||||||||||||||||||||||||||||||||||||||
| Journal or Publication Title: | Sci. Adv. | ||||||||||||||||||||||||||||||||||||||||
| Volume: | 8 | ||||||||||||||||||||||||||||||||||||||||
| Number: | 37 | ||||||||||||||||||||||||||||||||||||||||
| Date: | 2022 | ||||||||||||||||||||||||||||||||||||||||
| Publisher: | AMER ASSOC ADVANCEMENT SCIENCE | ||||||||||||||||||||||||||||||||||||||||
| Place of Publication: | WASHINGTON | ||||||||||||||||||||||||||||||||||||||||
| ISSN: | 2375-2548 | ||||||||||||||||||||||||||||||||||||||||
| Language: | English | ||||||||||||||||||||||||||||||||||||||||
| Faculty: | Unspecified | ||||||||||||||||||||||||||||||||||||||||
| Divisions: | Unspecified | ||||||||||||||||||||||||||||||||||||||||
| Subjects: | no entry | ||||||||||||||||||||||||||||||||||||||||
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| URI: | http://kups.ub.uni-koeln.de/id/eprint/68336 |
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