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Journal of Virology, November 2007, p. 11937-11945, Vol. 81, No. 21
0022-538X/07/$08.00+0     doi:10.1128/JVI.00942-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Astrovirus Increases Epithelial Barrier Permeability Independently of Viral Replication{triangledown}

Lindsey A. Moser,1 Michael Carter,2 and Stacey Schultz-Cherry1*

Department of Medical Microbiology and Immunology, University of Wisconsin—Madison, Madison, Wisconsin 53706,1 School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey GU2 7XH, United Kingdom2

Received 2 May 2007/ Accepted 7 August 2007

Astrovirus infection in a variety of species results in an age-dependent diarrhea; however, the means by which astroviruses cause diarrhea remain unknown. Studies of astrovirus-infected humans and turkeys have demonstrated few histological changes and little inflammation during infection, suggesting that intestinal damage or an overzealous immune response is not the primary mediator of astrovirus diarrhea. An alternative contributor to diarrhea is increased intestinal barrier permeability. Here, we demonstrate that astrovirus increases barrier permeability in a Caco-2 cell culture model system following apical infection. Increased permeability correlated with disruption of the tight-junction protein occludin and decreased the number of actin stress fibers in the absence of cell death. Additionally, permeability was increased when monolayers were treated with UV-inactivated virus or purified recombinant human astrovirus serotype 1 capsid in the form of virus-like particles. Together, these results demonstrate that astrovirus-induced permeability occurs independently of viral replication and is modulated by the capsid protein, a property apparently unique to astroviruses. Based on these data, we propose that the capsid contributes to diarrhea in vivo.

* Corresponding author. Mailing address: University of Wisconsin—Madison, Department of Medical Microbiology and Immunology, 1300 University Ave., 417 SMI, Madison, WI 53706. Phone: (608) 265-6462. Fax: (608) 262-8418. E-mail: slschul2{at}wisc.edu

{triangledown} Published ahead of print on 15 August 2007.

Journal of Virology, November 2007, p. 11937-11945, Vol. 81, No. 21
0022-538X/07/$08.00+0     doi:10.1128/JVI.00942-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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