Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural Ppublish 10 citations
PubMed: 37671751 DOI: 10.1002/jmv.29076
SARS-CoV-2 infection of polarized human airway epithelium induces necroptosis that causes airway epithelial barrier dysfunction.
J Med Virol 95(9):e29076
Authors: Siyuan Hao, Kang Ning, Cagla A Kuz, Min Xiong, Wei Zou, Soo Y Park, Shane McFarlin, Ziying Yan, Jianming Qiu
Affiliations
- Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, USA.
- Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA.
- Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa, USA.
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause the ongoing pandemic of coronavirus disease 2019 (COVID19). One key feature associated with COVID-19 is excessive pro-inflammatory cytokine production that leads to severe acute respiratory distress syndrome. Although the cytokine storm induces inflammatory cell death in the host, which type of programmed cell death mechanism that occurs in various organs and cells remains elusive. Using an in vitro culture model of polarized human airway epithelium (HAE), we observed that necroptosis, but not apoptosis or pyroptosis, plays an essential role in the damage of the epithelial barrier of polarized HAE infected with SARS-CoV-2. Pharmacological inhibitors of necroptosis, necrostatin-2 and necrosulfonamide, efficiently prevented cell death and epithelial barrier dysfunction caused by SARS-CoV-2 infection. Moreover, the silencing of genes that are involved in necroptosis, RIPK1, RIPK3, and MLKL, ameliorated airway epithelial damage of the polarized HAE infected with SARS-CoV-2. This study, for the first time, confirms that SARS-CoV-2 infection triggers necroptosis that disrupts the barrier function of human airway epithelia in vitro.
MeSH
Infections, Epithelium, Virology, Cells, Cell Death, Respiratory Distress Syndrome, Coronavirus, Sars Virus, Necroptosis, Covid-19, Sars-Cov-2
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