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J. Biol. Chem., Vol. 279, Issue 47, 48760-48766, November 19, 2004

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Acute Effects of Parainfluenza Virus on Epithelial Electrolyte Transport^*

Karl Kunzelmann, Jens König, Jane Sun, Daniel Markovich, Nicholas J. King, Guna Karupiah¶||, John A. Young**, and David I. Cook||**

From the ^**Department of Physiology, University of Sydney, New South Wales 2006, Australia, the Department of Physiology and Pharmacology, University of Queensland, Queensland 4072, Australia, the Department of Pathology, University of Sydney, New South Wales 2006, Australia, and the ^¶John Curtin School of Medical Research, Australian National University, Australian Capital Territory 2606, Australia

Parainfluenza viruses are important causes of respiratory disease in both children and adults. In particular, they are the major cause of the serious childhood illness croup (laryngotracheobronchitis). The infections produced by parainfluenza viruses are associated with the accumulation of ions and fluid in the respiratory tract. It is not known, however, whether this accumulation is because of a direct effect of the viruses on ion and fluid transport by the respiratory epithelium. Here we show that a model parainfluenza virus (the Sendai virus), in concentrations observed during respiratory infections, activates Cl^– secretion and inhibits Na⁺ absorption across the tracheal epithelium. It does so by binding to a neuraminidase-insensitive glycolipid, possibly asialo-GM1, triggering the release of ATP, which then acts in an autocrine fashion on apical P2Y receptors to produce the observed changes in ion transport. These findings indicate that fluid accumulation in the respiratory tract associated with parainfluenza virus infection is attributable, at least in part, to direct effects of the virus on ion transport by the respiratory epithelium.

Received for publication, August 25, 2004 , and in revised form, September 7, 2004.

^* This project was supported by the National Health and Medical Research Council of Australia, the Australian Research Council, Cystic Fibrosis Australia, and German Mukoviszidose e.V. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| Fellows of the Medical Foundation of the University of Sydney.

To whom correspondence should be addressed: Dept. of Physiology, School of Medical Sciences, Anderson Stuart Bldg. (F13), University of Sydney, NSW 2006, Australia.

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