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

  • 6 Citations

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
StatePublished - 1 Jul 2009

Fingerprint

Influenza A virus
Cations
Epithelial Cells
Lung
Infection
1-Phosphatidylinositol 4-Kinase
Human Influenza
Glucocorticoids
Lung Diseases
Phosphotransferases
Viruses
Proteins

Cite this

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. DOI: 10.1113/jphysiol.2009.171223

Gallacher, M.; Brown, Sean G.; Hale, B. G.; Fearns, R.; Olver, R. E.; Randall, R. E.; Wilson, S. M. / Cation currents in human airway epithelial cells induced by infection with influenza A virus.

In: Journal of Physiology, Vol. 587, No. 13, 01.07.2009, p. 3159-3173.

Research output: Contribution to journalArticle

@article{53785d5553534f7e96f3b176ce8a0ee4,
title = "Cation currents in human airway epithelial cells induced by infection with influenza A virus",
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.",
author = "M. Gallacher and Brown, {Sean G.} and Hale, {B. G.} and R. Fearns and Olver, {R. E.} and Randall, {R. E.} and Wilson, {S. M.}",
year = "2009",
month = "7",
doi = "10.1113/jphysiol.2009.171223",
volume = "587",
pages = "3159--3173",
journal = "Journal of Physiology",
issn = "0022-3751",
publisher = "Wiley-Blackwell",
number = "13",

}

Gallacher, M, Brown, SG, Hale, BG, Fearns, R, Olver, RE, Randall, RE & Wilson, SM 2009, 'Cation currents in human airway epithelial cells induced by infection with influenza A virus' Journal of Physiology, vol 587, no. 13, pp. 3159-3173. DOI: 10.1113/jphysiol.2009.171223

Cation currents in human airway epithelial cells induced by infection with influenza A virus. / Gallacher, M.; Brown, Sean G.; Hale, B. G.; Fearns, R.; Olver, R. E.; Randall, R. E.; Wilson, S. M.

In: Journal of Physiology, Vol. 587, No. 13, 01.07.2009, p. 3159-3173.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cation currents in human airway epithelial cells induced by infection with influenza A virus

AU - Gallacher,M.

AU - Brown,Sean G.

AU - Hale,B. G.

AU - Fearns,R.

AU - Olver,R. E.

AU - Randall,R. E.

AU - Wilson,S. M.

PY - 2009/7/1

Y1 - 2009/7/1

N2 - 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.

AB - 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.

U2 - 10.1113/jphysiol.2009.171223

DO - 10.1113/jphysiol.2009.171223

M3 - Article

VL - 587

SP - 3159

EP - 3173

JO - Journal of Physiology

T2 - Journal of Physiology

JF - Journal of Physiology

SN - 0022-3751

IS - 13

ER -

Gallacher M, Brown SG, Hale BG, Fearns R, Olver RE, Randall RE et al. Cation currents in human airway epithelial cells induced by infection with influenza A virus. Journal of Physiology. 2009 Jul 1;587(13):3159-3173. Available from, DOI: 10.1113/jphysiol.2009.171223