SARS-CoV-2 infection of polarized human airway epithelium induces necroptosis that causes airway epithelial barrier dysfunction

Siyuan Hao; Kang Ning; Cagla A Kuz; Min Xiong; Wei Zou; Soo Y Park; Shane McFarlin; Ziying Yan; Jianming Qiu

doi:10.1002/jmv.29076

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SARS-CoV-2 infection of polarized human airway epithelium induces necroptosis that causes airway epithelial barrier dysfunction

Journal article

Peer reviewed

SARS-CoV-2 infection of polarized human airway epithelium induces necroptosis that causes airway epithelial barrier dysfunction

Siyuan Hao, Kang Ning, Cagla A Kuz, Min Xiong, Wei Zou, Soo Y Park, Shane McFarlin, Ziying Yan and Jianming Qiu

Journal of medical virology, Vol.95(9), e29076

09/01/2023

DOI: 10.1002/jmv.29076

PMCID: PMC10754389

PMID: 37671751

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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.

Details

Title: Subtitle: SARS-CoV-2 infection of polarized human airway epithelium induces necroptosis that causes airway epithelial barrier dysfunction
Creators: Siyuan Hao - University of Kansas Medical Center
Kang Ning - University of Kansas Medical Center
Cagla A Kuz - University of Kansas Medical Center
Min Xiong - University of Kansas Medical Center
Wei Zou - University of Michigan
Soo Y Park - University of Iowa
Shane McFarlin - University of Kansas Medical Center
Ziying Yan - University of Iowa
Jianming Qiu - University of Kansas Medical Center
Resource Type: Journal article
Publication Details: Journal of medical virology, Vol.95(9), e29076
DOI: 10.1002/jmv.29076
PMID: 37671751
PMCID: PMC10754389
NLM abbreviation: J Med Virol
eISSN: 1096-9071
Grant note: DOI: 10.13039/100000060, name: National Institute of Allergy and Infectious Diseases, award: AI150877, AI151542
Language: English
Date published: 09/01/2023
Academic Unit: Anatomy and Cell Biology
Record Identifier: 9984461959702771

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