Forsyth Christopher B, Zhang Lijuan, Bhushan Abhinav, Swanson Barbara, Zhang Li, Mamede João I, Voigt Robin M, Shaikh Maliha, Engen Phillip A, Keshavarzian Ali
Department of Internal Medicine, Section of Gastroenterology, Rush Center for Integrated Microbiome and Chronobiology Research, Department of Anatomy and Cell Biology, Rush University Graduate College, Rush University Medical Center, Chicago, IL 60612, USA.
Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL 60612, USA.
Microorganisms. 2022 Oct 10;10(10):1996. doi: 10.3390/microorganisms10101996.
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.
2019年冠状病毒病（COVID-19）大流行于2020年1月在中国武汉爆发，一种名为严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的新型冠状病毒是其病原体。COVID-19疾病的主要死因迅速显现为急性呼吸窘迫综合征（ARDS）。ARDS的一个关键致病机制是“细胞因子风暴”，即血液中炎性细胞因子急剧增加。在大流行的最后两年，一些COVID-19幸存者出现了一种新的病理状况，出现了各种长期症状，这种情况被称为COVID-19急性后遗症（PASC）或“长新冠”。因此，迫切需要更好地了解该病毒的机制。病毒表面的刺突蛋白由相连的S1-S2亚基组成。当S1与人类细胞上的血管紧张素转换酶2（ACE2）受体结合时，S1亚基被切割，S2亚基介导病毒进入细胞。然后S1蛋白被释放到血液中，这可能是引发和/或持续细胞因子风暴的关键触发因素之一。在本研究中，我们检验了一个假设，即刺突蛋白S1足以激活炎症信号传导和细胞因子产生，且与病毒无关。我们的数据支持刺突蛋白S1在体外培养的人肺和肠上皮细胞中激活炎症信号传导和细胞因子产生方面可能发挥的作用。这些数据支持SARS-CoV-2刺突蛋白S1在COVID-19发病机制和PASC中可能发挥的作用。
