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

Abstract

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.

Rotavirus Disease Mechanisms Diarrhea, Vomiting and Inflammation : How and Why

“…Most of rotavirus permeability studies have been performed in vitro, on cell monolayers, which showed a disruption of tight junctions, decrease of transepithelial resistance 95,96 and increased transepithelial permeability to macromolecules 96 . The effect of paracellular leakage might be induced by NSP4 97 .…”

“…Moreover, Johansen et al 165 found that children with acute rotavirus infection excreted significantly less PEG of all sizes than control children and children with enteropathogenic Escherichia coli infections. Permeability studies performed in vitro, on cell monolayers, have however showed a disruption of tight junctions, decrease of transepithelial resistance 95,96 and increased transepithelial permeability to macromolecules 96 . The significant discrepancies between in vivo and in vitro studies is most likely due to the absence of hormone regulation, nerves and authentic non--transformed cells in the in vitro systems.…”

Metabolic Stress Boosts Humoral Responses In Vivo Independently of Inflammasome and Inflammatory Reaction

“…However, a series of observations suggest that pathogens can directly regulate metabolic responses. Rotavirus infection of an intestinal cell line (Caco-2) leads to metabolic dysfunction characterized by increased production of lactate, decreased mitochondrial function, and reduced intracellular ATP content (18). Viral mitochondria-localized inhibitor of apoptosis, a mitochondria-localizing protein encoded by the human CMV genome, also has been shown to inhibit ATP synthesis in infected cells, causing lower steady state ATP levels (19).…”

BUTYRATE SUPPLEMENTATION AFFECTS mRNA ABUNDANCE OF GENES INVOLVED IN GLYCOLYSIS, OXIDATIVE PHOSPHORYLATION AND LIPOGENESIS IN THE RUMEN EPITHELIUM OF HOLSTEIN DAIRY COWS

“…Infection by rotavirus of Caco-2 cells causes concurrent drops in transepithelial resistance and epithelial ATP concentrations (Dickman et al, 2000). In rumen epithelia, low mucosal pH and local ATP depletion are directly linked to increased epithelial permeability (Aschenbach et al, 2000).…”