炎症
细胞内
气道
势垒函数
免疫学
严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)
功能(生物学)
2019-20冠状病毒爆发
医学
2019年冠状病毒病(COVID-19)
化学
细胞生物学
生物
病理
外科
疾病
爆发
传染病(医学专业)
作者
Jian-Bang Xu,Wei‐Jie Guan,Yilin Zhang,Zhen Qiu,Lei Chen,Xiao-Chun Hou,Junqing Yue,Yunfan Zhou,Jie Shen,Lei Zhao,Yun-Xin Zhu,Jing Sun,Jincun Zhao,Wen‐Liang Zhou,Nanshan Zhong
标识
DOI:10.1038/s41392-024-01753-z
摘要
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection disrupts the epithelial barrier and triggers airway inflammation. The envelope (E) protein, a core virulence structural component of coronaviruses, may play a role in this process. Pathogens could interfere with transepithelial Cl − transport via impairment of the cystic fibrosis transmembrane conductance regulator (CFTR), which modulates nuclear factor κB (NF-κB) signaling. However, the pathological effects of SARS-CoV-2 E protein on airway epithelial barrier function, Cl − transport and the robust inflammatory response remain to be elucidated. Here, we have demonstrated that E protein down-regulated the expression of tight junctional proteins, leading to the disruption of the airway epithelial barrier. In addition, E protein triggered the activation of Toll-like receptor (TLR) 2/4 and downstream c-Jun N-terminal kinase (JNK) signaling, resulting in an increased intracellular Cl − concentration ([Cl − ] i ) via up-regulating phosphodiesterase 4D (PDE4D) expression in airway epithelial cells. This elevated [Cl − ] i contributed to the heightened airway inflammation through promoting the phosphorylation of serum/glucocorticoid regulated kinase 1 (SGK1). Moreover, blockade of SGK1 or PDE4 alleviated the robust inflammatory response induced by E protein. Overall, these findings provide novel insights into the pathogenic role of SARS-CoV-2 E protein in airway epithelial damage and the ongoing airway inflammation during SARS-CoV-2 infection.
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