Rotavirus alters paracellular permeability and energy metabolism in Caco-2 cells.
Rotaviruses infect epithelial cells of the small intestine, but the pathophysiology of the resulting severe diarrhea is incompletely understood. Histological 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 resistance (TER) in the absence of cell death. TER declined from 300 to 22 Omega. cm(2) between 8 and 24 h after infection and was accompanied by increased transepithelial permeability to macromolecules of 478 and 4,000 Da. Distribution of tight junction proteins claudin-1, occludin, and ZO-1 was significantly altered during infection. Claudin-1 redistribution was notably apparent at the onset of the decline in TER. Infection was associated with increased production of lactate, decreased mitochondrial oxygen consumption, and reduced cellular ATP (60% of control at 24 h after infection), conditions known to reduce the integrity of epithelial tight junctions. In conclusion, these data show that rotavirus infection of Caco-2 intestinal cells altered tight junction structure and function, which may be a response to metabolic dysfunction.
Dickman
K G
KG
Research Service, Department of Veterans Affairs Medical Center, Northport, New York 11768, USA.
Hempson
S J
SJ
Anderson
J
J
Lippe
S
S
Zhao
L
L
Burakoff
R
R
Shaw
R D
RD
D000818:Animals; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000502:physiology*; D062445:Claudin-1; D004734:Energy Metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000502:physiology / Q000821:virology; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D008253:Macaca mulatta; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D012401:Rotavirus / Q000502:physiology*
C568108:CLDN1 protein, human; D062445:Claudin-1; D007773:Lactates; D008565:Membrane Proteins; D010042:Ouabain