Effects of pH alteration on respiratory syncytial virus in human airway epithelial cells

Autor: Jessica L. Saunders, Ivana A. Daniels, Taiya L. Edwards, Ryan F. Relich, Yi Zhao, Laura A. Smith, Benjamin M. Gaston, Michael D. Davis
Rok vydání: 2023
Předmět:
Zdroj: ERJ Open Research. :00404-2022
ISSN: 2312-0541
DOI: 10.1183/23120541.00404-2022
Popis: Respiratory syncytial virus (RSV) is a leading cause of respiratory distress and hospitalization 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 if raising intracellular pH with Optate would decrease infection and replication of RSV in primary HAECs.We cultured HAECs from healthy subjects in both air-liquid interface (ALI) and submerged conditions. We infected HAECs with green fluorescent protein-labelled RSV (GFP-RSV; MOI 1) and treated them with Optate or phosphate buffered saline control. We collected supernatant after a four-hour incubation and then every 24 h. We used fluorescence intensity, fluorescent particle counts, plaque assays, western blots, and enzyme-linked immunosorbent assays (ELISA) to quantitate infection.In submerged culture, fluorescence intensity decreased in Optate-treated cells (48H p=0.0174, 72H p=viawestern blot and ELISA (pviaELISA (p=0.001). Additionally, RSV infection decreased as Optate concentration increased in a dose-dependent manner (pIn conclusion, Optate inhibits RSV infection in primary HAECs in a dose-dependent manner. These findings suggest Optate may have potential as an inhaled therapeutic for patients with RSV.
Databáze: OpenAIRE