SARS-CoV-2 nucleocapsid protein triggers hyperinflammation via protein-protein interaction-mediated intracellular Cl^- accumulation in respiratory epithelium.

ABSTRACT: SARS-CoV-2, the culprit pathogen of COVID-19, elicits prominent immune responses and cytokine storms. Intracellular Cl^- is a crucial regulator of host defense, whereas the role of Cl^- signaling pathway in modulating pulmonary inflammation associated with SARS-CoV-2 infection remains unclear. By using human respiratory epithelial cell lines, primary cultured human airway epithelial cells, and murine models of viral structural protein stimulation and SARS-CoV-2 direct challenge, we demonstrated that SARS-CoV-2 nucleocapsid (N) protein could interact with Smad3, which downregulated cystic fibrosis transmembrane conductance regulator (CFTR) expression via microRNA-145. The intracellular Cl^- concentration ([Cl^-]_i) was raised, resulting in p

SUBMITTER: Chen L 

PROVIDER: S-EPMC9328007 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature