Rhinovirus-16 increases ATP release in A549 cells without concomitant increase in production

Atkinson, Samantha K.; Morice, Alyn H.; Sadofsky, Laura R.

Abstract

Human rhinovirus (RV) is the most common cause of upper respiratory tract infection (URTI) and chronic airway disease exacerbation. Cough is present in 50–80% of URTI cases, accompanied by heightened airway hypersensitivity, yet no effective treatment currently exists for this infectious cough. The mechanism by which RV causes cough and airway hypersensitivity in URTI is still unknown despite recent advances in potential therapies for chronic cough. The effect of RV-16 infection (MOI 1) on intracellular ATP stores and ATP release in A549 alveolar epithelial cells was measured. RV-16 infection was found to significantly increase (by 50% from basal at 24 h) followed by decrease (by 50% from basal at 48 and 72 h) intracellular ATP concentrations, while increasing ATP release (from 72 h) independently of secondary stimulation. This effect was mimicked by intercellular adhesion molecule 1 receptor binding alone through ultraviolet-inactivated sham control. In addition, RV-16-infected cells became more sensitive to secondary stimulation with both hypotonic and isotonic solutions, suggestive of a hypersensitive response. These responses were not mediated via increased TRPV4 or pannexin-1 whole-cell expression as determined by Western blotting. Interestingly, the increased ATP release seen was not a result of increased mitochondrial ATP production. Thus, this is the first report demonstrating that RV-16 infection of airway epithelial cells causes hypersensitivity by increasing ATP release. These finding provide a novel insight into the process by which viruses may cause cough and identify a potential target for treatment of viral and post-viral cough.

Citation

Atkinson, S. K., Morice, A. H., & Sadofsky, L. R. (2020). Rhinovirus-16 increases ATP release in A549 cells without concomitant increase in production. ERJ Open Research, 6(4), Article 00159-2020. https://doi.org/10.1183/23120541.00159-2020

• Journal Article Type: Article
• Acceptance Date: Jul 8, 2020
• Online Publication Date: Oct 19, 2020
• Publication Date: 2020-10
• Deposit Date: Oct 21, 2020
• Publicly Available Date: Oct 22, 2020
• Journal: ERJ Open Research
• Electronic ISSN: 2312-0541
• Publisher: European Respiratory Society
• Peer Reviewed: Peer Reviewed
• Volume: 6
• Issue: 4
• Article Number: 00159-2020
• DOI: https://doi.org/10.1183/23120541.00159-2020
• Public URL: https://hull-repository.worktribe.com/output/3645899
• Publisher URL: https://openres.ersjournals.com/content/6/4/00159-2020