Rotavirus-induced structural and functional alterations in tight junctions of polarized intestinal Caco-2 cell monolayers.
We provide here new insights into rotavirus (RRV) pathogenicity by showing that RRV infection promotes structural and functional injuries localized at the tight junctions (TJ) in the cell-cell junctional complex of cultured polarized human intestinal Caco-2 cells forming monolayers. RRV infection resulted in a progressive increase in the paracellular permeability to [(3)H]mannitol as a function of the time postinfection. We observed a disorganization of the TJ-associated protein occludin as a function of the time postinfection, whereas distribution of the zonula adherens associated E-cadherin was not affected. These structural and functional RRV-induced TJ injuries were not accompanied by alteration in cell and monolayer integrity, as assessed by the lack of change in transepithelial membrane resistance and lactate dehydrogenase release. Finally, using the stabilizer of actin filaments Jasplakinolide, we demonstrated that the RRV-induced structural and functional alterations in TJ are independent of the RRV-induced apical F-actin rearrangements.
Obert
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Unité 510, Pathogènes et Fonctions des Cellules Epithéliales Polarisées, Institut National de la Santé et de la Recherche Médicale, Faculté de Pharmacie, Université Paris XI, 92296 Châtenay-Malabry, France.
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D018938:Caco-2 Cells; D015820:Cadherins / Q000378:metabolism; D002463:Cell Membrane Permeability; D016764:Cell Polarity; D003599:Cytoskeleton / Q000648:ultrastructure; D006801:Humans; D007413:Intestinal Mucosa / Q000502:physiology / Q000648:ultrastructure / Q000821:virology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D062793:Occludin; D012401:Rotavirus / Q000472:pathogenicity* / Q000502:physiology; D019108:Tight Junctions / Q000502:physiology* / Q000648:ultrastructure* / Q000821:virology
D015820:Cadherins; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D007770:L-Lactate Dehydrogenase