Effect of rotavirus infection on intracellular calcium homeostasis in cultured cells.

The effect of rotavirus infection on intracellular [Ca2+] was studied in a model system (MA-104 cells). In cells infected at high multiplicity with the OSU strain of rotavirus, production of infectious viruses was maximal at 6 hr postinfection. Cell death, as measured by incorporation of ethidium bromide, started at 6 hr and was complete at 15 hr postinfection. At 4 hr postinfection, intracellular [Ca2+], measured by quin2 fluorescence, was not modified, but Ca2+ permeability was increased. With progression of the infection, intracellular [Ca2+] and Ca2+ pools increased due to the failure of regulatory mechanisms to compensate increased Ca2+ entry. These effects were blocked by cycloheximide added up to 5 hr postinfection, but not by actinomycin D. Reduced extracellular [Ca2+] afforded protection of cell death induced by infection, under conditions at which production of infectious viruses was not affected. The cytopathic effect of rotavirus on host cells appears to be mediated by an increase in intracellular [Ca2+] induced by the synthesis of a viral product. The failure of ionic homeostasis of the enterocyte might be involved in the development of diarrhea.