Inhibition of airway Na⁺ transport by respiratory syncytial virus

Institut für Physiologie, Universität Regensburg, Universitätstrasse 31, D-93053 Regensburg, Germany; School of Biomedical Sciences, Department of Physiology and Pharmacology, University of Queensland, St Lucia, QLD 4072, Australia; Department of Respiratory Medicine and Sleep, Monash Medical Centre, 246 Clayton

	Abstract

In previous studies we have shown that two major respiratory pathogens, influenza virus and parainfluenza virus, produce acute alterations in ion transport on contacting the apical membrane of 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 through 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 IBMX, it is not due to a non-specific 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 (10²-10⁵pfu/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.