Rotavirus alters paracellular permeability and energy metabolism in Caco-2cells

Rotaviruses infect epithelial cells of the small intestine, but the pathoph ysiology of the resulting severe diarrhea is incompletely understood. Histo logical damage to intestinal epithelium is not a consistent feature, and in vitro studies showed that intestinal cells did not undergo rapid death and lysis during viral replication. We show that rotavirus infection of Caco-2 cells caused disruption of tight junctions and loss of transepithelial res istance (TER) in the absence of cell death. TER declined from 300 to 22 Ome ga . cm(2) between 8 and 24 h after infection and was accompanied by increa sed transepithelial permeability to macromolecules of 478 and 4,000 Da. Dis tribution of tight junction proteins claudin-1, occludin, and ZO-1 was sign ificantly altered during infection. Claudin-1 redistribution was notably ap parent at the onset of the decline in TER. Infection was associated with in creased production of lactate, decreased mitochondrial oxygen consumption, and reduced cellular ATP (60% of control at 24 h after infection), conditio ns known to reduce the integrity of epithelial tight junctions. In conclusi on, these data show that rotavirus infection of Caco-2 intestinal cells alt ered tight junction structure and function, which may be a response to meta bolic dysfunction.