title: NSP4 enterotoxin of rotavirus induces paracellular leakage in polarized epithelial cells.
abstract: 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.
authors.affiliation: Division of Medical Microbiology, Department of Health and Environment, Linköping University, Linköping, Sweden.
authors.forename: F
authors.initials: F
authors.lastname: Tafazoli
authors.forename: C Q
authors.initials: CQ
authors.lastname: Zeng
authors.forename: M K
authors.initials: MK
authors.lastname: Estes
authors.forename: K E
authors.initials: KE
authors.lastname: Magnusson
authors.forename: L
authors.initials: L
authors.lastname: Svensson
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002463:Cell Membrane Permeability; D016764:Cell Polarity; D012321:DNA-Directed RNA Polymerases; D003911:Dextrans / Q000493:pharmacokinetics; D004285:Dogs; D017097:Electric Impedance; D004768:Enterotoxins / Q000633:toxicity*; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D008565:Membrane Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D012401:Rotavirus / Q000472:pathogenicity*; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000633:toxicity*; D062826:Zonula Occludens-1 Protein
chemical_list: D000199:Actins; D003911:Dextrans; D004768:Enterotoxins; D008565:Membrane Proteins; D010750:Phosphoproteins; D017361:Viral Nonstructural Proteins; D062826:Zonula Occludens-1 Protein; C015219:fluorescein isothiocyanate dextran; D012321:DNA-Directed RNA Polymerases; D016650:Fluorescein-5-isothiocyanate