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

Michael Gallacher, Sean Brown, B. G. Hale, R. Fearns, Richard Olver, R. E. Randall, Stuart 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

    Keywords

    • CHANNEL ALPHA-SUBUNIT
    • LEUCINE-ZIPPER PROTEIN
    • NA+ CHANNEL
    • NS1 PROTEIN
    • GLUCOCORTICOID HORMONE
    • LIQUID HOMEOSTASIS
    • DIRECT ACTIVATION
    • SODIUM-TRANSPORT
    • FLUID CLEARANCE
    • SURFACE LIQUID

    Cite this

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