Cardiac glycosides decrease influenza virus replication by inhibiting cell protein translational machinery

Luciano Amarelle, Jeremy Katzen, Masahiko Shigemura, Lynn C. Welch, Héctor Cajigas, Christin Peteranderl, Diego Celli, Susanne Herold, Emilia Lecuona, Jacob I Sznajder

Research output: Contribution to journalArticle

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-α1 resistant to CGs. Thus we utilized Na-K-ATPase-α1-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.

Original languageEnglish (US)
Pages (from-to)L1094-L1106
JournalAmerican journal of physiology. Lung cellular and molecular physiology
Volume316
Issue number6
DOIs
StatePublished - Jun 1 2019

Fingerprint

Cardiac Glycosides
Virus Replication
Orthomyxoviridae
Influenza A virus
Ouabain
Proteins
Alveolar Epithelial Cells
RNA Stability
Protein Biosynthesis
Human Influenza
Proteolysis
Rodentia
Potassium
Heart Failure
Calcium
Lung
sodium-translocating ATPase

Keywords

  • Na-K-ATPase
  • antiviral treatment
  • intracellular potassium

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

Amarelle, Luciano ; Katzen, Jeremy ; Shigemura, Masahiko ; Welch, Lynn C. ; Cajigas, Héctor ; Peteranderl, Christin ; Celli, Diego ; Herold, Susanne ; Lecuona, Emilia ; Sznajder, Jacob I. / Cardiac glycosides decrease influenza virus replication by inhibiting cell protein translational machinery. In: American journal of physiology. Lung cellular and molecular physiology. 2019 ; Vol. 316, No. 6. pp. L1094-L1106.
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Cardiac glycosides decrease influenza virus replication by inhibiting cell protein translational machinery. / Amarelle, Luciano; Katzen, Jeremy; Shigemura, Masahiko; Welch, Lynn C.; Cajigas, Héctor; Peteranderl, Christin; Celli, Diego; Herold, Susanne; Lecuona, Emilia; Sznajder, Jacob I.

In: American journal of physiology. Lung cellular and molecular physiology, Vol. 316, No. 6, 01.06.2019, p. L1094-L1106.

Research output: Contribution to journalArticle

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AU - Amarelle, Luciano

AU - Katzen, Jeremy

AU - Shigemura, Masahiko

AU - Welch, Lynn C.

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AU - Peteranderl, Christin

AU - Celli, Diego

AU - Herold, Susanne

AU - Lecuona, Emilia

AU - Sznajder, Jacob I

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