Journal article

Publication year: 2019

Pages: L1094-L1106

Journal: American Journal of Physiology - Lung Cellular and Molecular Physiology

Volume number: 316

Issue number: 6

ISSN: 1040-0605

eISSN: 1522-1504

Open access status: Green

DOI Link: https://doi.org/10.1152/ajplung.00173.2018

Publisher: American Physiological Society

Abstract: 
Cardiac glycosides (CGs) are used primarily for cardiac failure and have been reported to have other effects, including inhibition of viral replication. Here we set out to study mechanisms by which CGs as inhibitors of the Na-K-ATPase decrease influenza A virus (IAV) replication in the lungs. We found that CGs inhibit influenza virus replication in alveolar epithelial cells by decreasing intracellular potassium, which in turn inhibits protein translation, independently of viral entry, mRNA transcription, and protein degradation. These effects were independent of the Src signaling pathway and intracellular calcium concentration changes. We found that short-term treatment with ouabain prevented IAV replication without cytotoxicity. Rodents express a Na-K-ATPase-alpha 1 resistant to CGs. Thus we utilized Na-K-ATPase-alpha(1)-sensitive mice, infected them with high doses of influenza virus, and observed a modest survival benefit when treated with ouabain. In summary. we provide evidence that the inhibition of the Na-K-ATPase by CGs decreases influenza A viral replication by modulating the cell protein translational machinery and results in a modest survival benefit in mice.

Harvard Citation style: Amarelle, L., Katzen, J., Shigemura, M., Welch, L., Cajigas, H., Peteranderl, C., et al. (2019) Cardiac glycosides decrease influenza virus replication by inhibiting cell protein translational machinery, American Journal of Physiology - Lung Cellular and Molecular Physiology, 316(6), pp. L1094-L1106. https://doi.org/10.1152/ajplung.00173.2018

APA Citation style: Amarelle, L., Katzen, J., Shigemura, M., Welch, L., Cajigas, H., Peteranderl, C., Celli, D., Herold, S., Lecuona, E., & Sznajder, J. (2019). Cardiac glycosides decrease influenza virus replication by inhibiting cell protein translational machinery. American Journal of Physiology - Lung Cellular and Molecular Physiology. 316(6), L1094-L1106. https://doi.org/10.1152/ajplung.00173.2018