Cation currents in human airway epithelial cells induced by infection with influenza A virus

M. Gallacher, Sean G. Brown, B. G. Hale, R. Fearns, R. E. Olver, R. E. Randall, S. M. Wilson

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Influenza A viruses cause lung disease via an incompletely understood mechanism that involves the accumulation of liquid within the lungs. The accumulation of lung liquid is normally prevented by epithelial Na(+) absorption, a transport process regulated via several pathways including phosphoinositide-3-kinase (PI3K). Since the influenza A virus encodes a non-structural protein (NS1) that can activate this kinase, we now explore the effects of NS1 upon the biophysical properties of human airway epithelial cells. Transient expression of NS1 depolarized electrically isolated cells maintained in glucocorticoid-free medium by activating a cation conductance identical to the glucocorticoid-induced conductance seen in single cells. This response involved PI3K-independent and PI3K-dependent mechanisms. Infecting glucocorticoid-deprived cells with influenza A virus disrupted the normal electrical coupling between neighbouring cells, but also activated a conductance identical to that induced by NS1. This response to virus infection was only partially dependent upon NS1-mediated activation of PI3K. The presence of NS1 allows influenza A to modify the biophysical properties of infected cells by activating a Na(+)-permeable conductance. Whilst the activation of Na(+)-permeable channels may be expected to increase the rate of Na(+) absorption and thus reduce the volume of liquid in the lung, liquid does normally accumulate in influenza A-infected lungs. The overall effect of influenza A on lung liquid volume may therefore reflect a balance between the activation and inhibition of Na(+)-permeable channels.
Original languageEnglish
Pages (from-to)3159-3173
Number of pages15
JournalJournal of Physiology
Volume587
Issue number13
DOIs
Publication statusPublished - 1 Jul 2009

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    Gallacher, M., Brown, S. G., Hale, B. G., Fearns, R., Olver, R. E., Randall, R. E., & Wilson, S. M. (2009). Cation currents in human airway epithelial cells induced by infection with influenza A virus. Journal of Physiology, 587(13), 3159-3173. https://doi.org/10.1113/jphysiol.2009.171223