Neuregulin-1 reduces human airway epithelium permeability caused by respiratory viral infection through HER-2 3594
Year: 2025
Type: article
Abstract: Description Respiratory viral infections with negative-strand RNA viruses, like influenza A virus (IAV) and respiratory syncytial virus (RSV) cause significant morbidity and mortality. Previously we demonstrated mice treated with neuregulin-1 (NRG1) survived normally lethal infections with IAV or Sendai virus, a rodent virus related to RSV. Using well-differentiated human airway epithelial cells (hBEC) grown at air-liquid interface and infected with RSV, NRG-1 reduced viral titer and epithelial leak, which might explain increased survival following a severe respiratory viral infection. NRG1 binds three receptors of the EGFR family (HER-2 (ERbB2), ErbB3, and ErbB4) and signals through homo or heterodimers consisting of two ErbB receptors. To determine which ErbB receptors are necessary for NRG1’s function in vitro, we added mAbs against each of the ErbB receptors to the basolateral compartment of hBECs along with NRG1 (100 ng) for 5 days before gfp-RSV inoculation. Viral titer was determined by quantifying GFP by fluorescent microscopy 48h post-inoculation (PI) RSV. Epithelial leakage was determined by treating the transwell apical side with 70 KDa FITC-Dextran (25 mcg) and collecting basal media for spectrophotometric analysis at day 4 PI. Blocking HER-2 but not other ErbB receptors significantly increased viral titer and permeability, suggesting HER-2 is the primary receptor for NRG1 signaling and protection from viral insult in airway epithelium. Funding Sources This work was supported by NIH grant R01AI171027 (to Mitchell H Grayson) Topic Categories Translational and Interventional Immunology (TI)
Source: The Journal of Immunology
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funder: National Institutes of Health
OpenAlex ID: W4416448422
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