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Effects of pH alteration on respiratory syncytial virus in human airway epithelial cells.
Saunders, Jessica L; Daniels, Ivana A; Edwards, Taiya L; Relich, Ryan F; Zhao, Yi; Smith, Laura A; Gaston, Benjamin M; Davis, Michael D.
Afiliação
  • Saunders JL; Division of Pulmonology, Allergy and Sleep Medicine, Riley Hospital for Children, Indianapolis, IN, USA.
  • Daniels IA; Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Edwards TL; Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Relich RF; Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Zhao Y; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Smith LA; Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Gaston BM; Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Davis MD; Division of Pulmonology, Allergy and Sleep Medicine, Riley Hospital for Children, Indianapolis, IN, USA.
ERJ Open Res ; 9(4)2023 Jul.
Article em En | MEDLINE | ID: mdl-37465558
Background: Respiratory syncytial virus (RSV) is a leading cause of respiratory distress and hospitalisation in the paediatric population. Low airway surface pH impairs antimicrobial host defence and worsens airway inflammation. Inhaled Optate safely raises airway surface pH in humans and raises intracellular pH in primary human airway epithelial cells (HAECs) in vitro. We aimed to determine whether raising intracellular pH with Optate would decrease infection and replication of RSV in primary HAECs. Methods: We cultured HAECs from healthy subjects in both air-liquid interface and submerged conditions. We infected HAECs with green fluorescent protein-labelled RSV (GFP-RSV; multiplicity of infection=1) and treated them with Optate or PBS control. We collected supernatant after a 4-h incubation and then every 24 h. We used fluorescence intensity, fluorescent particle counts, plaque assays, Western blots and ELISA to quantitate infection. Results: In submerged culture, fluorescence intensity decreased in Optate-treated cells (48 h p=0.0174, 72 h p≤0.001). Similarly, Optate treatment resulted in decreased fluorescent particle count (48 h p=0.0178, 72 h p=0.0019) and plaque-forming units (48 h p=0.0011, 72 h p=0.0148) from cell culture supernatant. In differentiated HAECs cultured at ALI, Optate treatment decreased fluorescence intensity (p≤0.01), GFP via Western blot and ELISA (p<0.0001), and RSV-fusion protein via ELISA (p=0.001). Additionally, RSV infection decreased as Optate concentration increased in a dose-dependent manner (p<0.001). Conclusions: Optate inhibits RSV infection in primary HAECs in a dose-dependent manner. These findings suggest that Optate may have potential as an inhaled therapeutic for patients with RSV.

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: ERJ Open Res Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: ERJ Open Res Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos