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Inhibition of Airway Na⁺ Transport by Respiratory Syncytial Virus

Institut für Physiologie, Universität Regensburg, Universitätstrasse 31, D-93053 Regensburg, Germany,¹ School of Biomedical Sciences, Department of Physiology and Pharmacology, University of Queensland, St. Lucia, QLD 4072, Australia,² Department of Respiratory Medicine and Sleep, Monash Medical Centre, 246 Clayton Rd., Clayton, VIC 3168, Australia,³ Department of Pathology, University of Sydney, NSW 2006, Australia,⁴ Department of Physiology, University of Sydney, NSW 2006, Australia⁵

Received 28 November 2006/ Accepted 30 January 2007

In previous studies, we have shown that two major respiratory pathogens, influenza virus and parainfluenza virus, produce acute alterations in ion transport upon contacting the apical membrane of the respiratory epithelium. In the present study, we examine the effects on ion transport by the mouse tracheal epithelium of a third major respiratory pathogen, respiratory syncytial virus (RSV). RSV infections are associated with fluid accumulation in the respiratory tract and cause illnesses that range in severity from rhinitis, sinusitis, otitis media, and bronchitis to bronchiolitis and pneumonia. We find that within minutes of RSV contacting the apical membrane; it inhibits amiloride-sensitive Na⁺ transport by the epithelium. This effect is mediated by protein kinase C and is reproduced by recombinant viral F (fusion) protein. Since this inhibition is not accompanied by any alteration in the epithelial responses to carbachol or to forskolin plus 3-isobutyl-1-methylxanthine (IBMX), it is not due to a nonspecific toxic action of the virus. The inhibition also appears to require Toll-like receptor 4 and the presence of asialogangliosides in the apical membrane. Since the concentration range over which this inhibition is observed (10² to 10⁵ PFU/ml) is comparable to the viral concentrations observed in clinical and experimental RSV infections, it seems likely that direct inhibition by the virus of epithelial Na⁺ transport may contribute to the fluid accumulation that is observed in RSV infections.

Published ahead of print on 7 February 2007.

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