title: Changes in macromolecular transport appear early in Caco-2 cells infected with a human rotavirus.
abstract: OBJECTIVE
  Rotavirus is a major cause of viral gastroenteritis, but its interaction with intestinal mucosa is poorly understood. The aim of this study was to examine the effect of Wa rotavirus (VP7 serotype 1) on barrier function in confluent Caco-2 cell monolayers. Wa is the most common serotype causing severe diarrhoea in humans. MATERIAL AND METHODS. We examined light and electron microscopic morphology, macromolecular transport, paracellular permeability, electrical parameters, disaccharidases and cytoskeletal structure in Wa- and in control sham-infected cells using a homologous human virus-cell system resembling human infection.
  
  
  RESULTS
  During the first 48 h following Wa infection, there was no evidence of loss of integrity or of cytopathic effect in the monolayer. A significant cytopathic effect was noticed after 48 h. Further studies examined the initial 24-h period during which there was no evidence of significant injury. Apical-to-basolateral transcytosis of the macromolecule horseradish peroxidase (HRP) was selectively inhibited at 4 and 24 h post-infection with Wa. There were no significant changes in basolateral-to-apical transcytosis, endocytosis or in apical-to-apical recycling of HRP after Wa infection. G- and F-actin levels were significantly reduced within an area corresponding to the viroplasm in Wa-infected cells but not elsewhere in the monolayer.
  
  
  CONCLUSIONS
  The early stages of rotavirus infection, before gross epithelial injury, are associated with a selective reduction in the apical uptake and transcytosis of macromolecules. We speculate that this is an epithelial defence mechanism.
authors.affiliation: Department of Gastroenterology and Clinical Nutrition, Royal Children's Hospital, Melbourne, Australia. tony.cattosmith@rch.org.au
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Catto-Smith
authors.forename: Sarah
authors.initials: S
authors.lastname: Emselle
authors.forename: Ruth F
authors.initials: RF
authors.lastname: Bishop
mesh_terms: D000199:Actins / Q000378:metabolism*; D001693:Biological Transport, Active; D018938:Caco-2 Cells / Q000648:ultrastructure / Q000821:virology; D002463:Cell Membrane Permeability / Q000502:physiology*; D003599:Cytoskeleton / Q000648:ultrastructure; D004187:Disaccharides / Q000378:metabolism; D006735:Horseradish Peroxidase / Q000378:metabolism*; D006801:Humans; D008854:Microscopy, Electron; D012401:Rotavirus / Q000472:pathogenicity*; D012400:Rotavirus Infections / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D019108:Tight Junctions / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D000199:Actins; D004187:Disaccharides; D006735:Horseradish Peroxidase