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Journal of Virology, February 2001, p. 1540-1546, Vol. 75, No. 3
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.3.1540-1546.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

NSP4 Enterotoxin of Rotavirus Induces Paracellular Leakage in Polarized Epithelial Cells

Farideh Tafazoli,1 Carl Q. Zeng,2 Mary K. Estes,2 Karl-Erik Magnusson,1 and Lennart Svensson3,*

Division of Medical Microbiology, Department of Health and Environment, Linköping University, Linköping,1 and Department of Virology, Swedish Institute for Infectious Disease Control (SMI), Karolinska Institute, Solna,3 Sweden, and Division of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas2

Received 27 July 2000/Accepted 7 November 2000

The nonstructural NSP4 protein of rotavirus has been described as the first viral enterotoxin. In this study we have examined the effect of NSP4 on polarized epithelial cells (MDCK-1) grown on permeable filters. Apical but not basolateral administration of NSP4 was found to cause a reduction in the transepithelial electrical resistance, redistribution of filamentous actin, and an increase in paracellular passage of fluorescein isothiocyanate-dextran. Significant effects on transepithelial electrical resistance were noted after a 20- to 30-h incubation with 1 nmol of NSP4. Most surprisingly, the epithelium recovered its original integrity and electrical resistance upon removal of NSP4. Preincubation of nonconfluent MDCK-1 cells with NSP4 prevented not only development of a permeability barrier but also lateral targeting of the tight-junction-associated Zonula Occludens-1 (ZO-1) protein. Taken together, these data indicate new and specific effects of NSP4 on tight-junction biogenesis and show a novel effect of NSP4 on polarized epithelia.

* Corresponding author. Mailing address: Dept. of Virology, Swedish Institute for Infectious Disease Control (SMI), 171 82 Solna, Sweden. Phone: 46 8 457 26 96. Fax: 46 8 30 16 35. E-mail: lensve{at}mbox.ki.se.

Journal of Virology, February 2001, p. 1540-1546, Vol. 75, No. 3
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.3.1540-1546.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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