SARS-CoV-2 infection of polarized human airway epithelium induces necroptosis that causes airway epithelial barrier dysfunction.
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ABSTRACT:
SUBMITTER: Hao S
PROVIDER: S-EPMC10754389 | biostudies-literature | 2023 Sep
REPOSITORIES: biostudies-literature
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SARS-CoV-2 infection of polarized human airway epithelium induces necroptosis that causes airway epithelial barrier dysfunction.
Hao Siyuan S Ning Kang K Ning Kang K Kuz Cagla A CA Xiong Min M Zou Wei W Park Soo Y SY McFarlin Shane S Yan Ziying Z Qiu Jianming J
Journal of medical virology 20230901 9
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 polari ...[more]
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Project description:Secondary bacterial infection following rhinovirus (RV) infection has been recognized in chronic obstructive pulmonary disease.We sought to understand mechanisms by which RV infection facilitates secondary bacterial infection.Primary human airway epithelial cells grown at air-liquid interface and human bronchial epithelial (16HBE14o-) cells grown as polarized monolayers were infected apically with RV. Transmigration of bacteria (nontypeable Haemophilus influenzae and others) was assessed by colony counting and transmission electron microscopy. Transepithelial resistance (R(T)) was measured by using a voltmeter. The distribution of zona occludins (ZO)-1 was determined by immunohistochemistry and immunoblotting.Epithelial cells infected with RV showed 2-log more bound bacteria than sham-infected cultures, and bacteria were recovered from the basolateral media of RV- but not sham-infected cells. Infection of polarized airway epithelial cell cultures with RV for 24 hours caused a significant decrease in R(T) without causing cell death or apoptosis. Ultraviolet-treated RV did not decrease R(T), suggesting a requirement for viral replication. Reduced R(T) was associated with increased paracellular permeability, as determined by flux of fluorescein isothiocyanate (FITC)-inulin. Neutralizing antibodies to tumor necrosis factor (TNF)-alpha, IFN-gamma and IL-1beta reversed corresponding cytokine-induced reductions in R(T) but not that induced by RV, indicating that the RV effect is independent of these proinflammatory cytokines. Confocal microscopy and immunoblotting revealed the loss of ZO-1 from tight junction complexes in RV-infected cells. Intranasal inoculation of mice with RV1B also caused the loss of ZO-1 from the bronchial epithelium tight junctions in vivo.RV facilitates binding, translocation, and persistence of bacteria by disrupting airway epithelial barrier function.
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