期刊
MICROORGANISMS
卷 10, 期 10, 页码 -出版社
MDPI
DOI: 10.3390/microorganisms10101996
关键词
COVID-19; ARDS; cytokine storm; S1 spike protein; SARS-CoV-2; PASC; ACE2; A549 cells; Caco-2 cells
类别
资金
- NSF Collaborative Research: RAPID grant [2031754]
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [2031754] Funding Source: National Science Foundation
The COVID-19 pandemic originated in Wuhan, China in 2020 and led to numerous deaths and long-term symptoms in survivors. Research suggests that the spike protein S1 on the surface of the virus may play a significant role in the pathogenesis of COVID-19 and the development of long-term symptoms.
The coronavirus disease 2019 (COVID-19) pandemic began in January 2020 in Wuhan, China, with a new coronavirus designated SARS-CoV-2. The principal cause of death from COVID-19 disease quickly emerged as acute respiratory distress syndrome (ARDS). A key ARDS pathogenic mechanism is the Cytokine Storm, which is a dramatic increase in inflammatory cytokines in the blood. In the last two years of the pandemic, a new pathology has emerged in some COVID-19 survivors, in which a variety of long-term symptoms occur, a condition called post-acute sequelae of COVID-19 (PASC) or Long COVID. Therefore, there is an urgent need to better understand the mechanisms of the virus. The spike protein on the surface of the virus is composed of joined S1-S2 subunits. Upon S1 binding to the ACE2 receptor on human cells, the S1 subunit is cleaved and the S2 subunit mediates the entry of the virus. The S1 protein is then released into the blood, which might be one of the pivotal triggers for the initiation and/or perpetuation of the cytokine storm. In this study, we tested the hypothesis that the S1 spike protein is sufficient to activate inflammatory signaling and cytokine production, independent of the virus. Our data support a possible role for the S1 spike protein in the activation of inflammatory signaling and cytokine production in human lung and intestinal epithelial cells in culture. These data support a potential role for the SARS-CoV-2 S1 spike protein in COVID-19 pathogenesis and PASC.
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