Active viremia in rotavirus-infected mice

Abstract

Rotavirus circulates extraintestinally in animals used as models for rotavirus infection and in children. Rotavirus infection in mice was used to define host or viral factors that affect rotavirus viremia. Antigenemia was observed with homologous and heterologous rotaviruses, and neither age nor mouse strain genetics altered the occurrence of rotavirus antigenemia or viremia. Rotavirus RNA and infectious virus were present in sera and associated with the plasma fraction of blood in all infected mice. These findings indicate that antigenemia/viremia occurs routinely in rotavirus infections and imply that infectious rotavirus has access to any extraintestinal cell within contact of blood.

FIG. 1.

Rotavirus antigenemia is not rotavirus strain dependent. Rotavirus naïve adult CD-1 mice were orally inoculated on day 0 with the indicated strains of rotavirus. Mice were sacrificed at the indicated time points and 10% (wt/vol) fecal suspensions (squares and circles) and undiluted sera (open diamonds and open triangles) analyzed for rotavirus antigens by ELISA. Points represent average values for each time point (n = 3 to 5). A. Mice were inoculated with either 10 ID₅₀ (dashed lines) or 10⁵ ID₅₀ (solid lines) EC_wt. B. Mice were inoculated with 10⁴ ID₅₀ EDIM. C. Mice were inoculated with 10 ID₅₀ RRV. The gray box indicates mice inoculated with inactivated RRV (n = 3).

FIG. 2.

Detection of rotavirus antigens. A. Six litters of 5-day-old naïve CD-1 pups were randomized (6 to 8 mice/litter) and administered either phosphate-buffered saline (PBS) (white bars, n = 3 litters) or 10⁵ ID₅₀ EC_wt (black bars, n = 3 litters). Four days after inoculation, the intestines and the blood from each litter were pooled, gut homogenates or sera recovered, respectively, and samples analyzed for rotavirus antigens by ELISA. Bars represent average values of samples pooled from each of three litters ± the standard deviation. B. Naïve adult CD-1 mice were orally inoculated with 10⁵ ID₅₀ EC_wt (black bars) or PBS (white bars). Three days after inoculation, whole blood was collected in EDTA-containing collection tubes for each mouse to prevent clotting. Cells were recovered by low-speed centrifugation after a washing and cell lysates made by addition of 150 μl PBS to each tube followed by three freeze-thaw cycles. Plasma and cell fractions were analyzed by ELISA for the presence of rotavirus antigens. Each bar represents the average value from three mice ± the standard deviation.