The effects of host age, virus dose, and virus strain on heterologous rotavirus infection of suckling mice

Abstract

Seven-day-old suckling CD-1 mice, born to seronegative dams, were orally inoculated with a number of animal and human rotaviruses. Simian (SA11), rhesus (RRV), and bovine (B223) rotaviruses were found to replicate and cause severe disease. Canine (K9), bovine (B641), and human (Wa) rotaviruses either replicated minimally and caused minimal disease (K9, B641) or failed to replicate or cause disease (Wa). The features of SA11 infection of mice were examined in greater detail. Suckling mice were susceptible to infection and disease from 1 day of age to 13-15 days of age. Restriction of disease occurred at an earlier age (13 days) than restriction of replication (15 days). Dose-response studies in seven-day-old mice showed that virus replication and disease could be induced with doses as low as 1 x 10(2) pfu/mouse; however, both intestinal virus titers and severity of disease increased in parallel with virus dose. Intestinal virus replication appeared to be restricted in SA11 infections. Only at very low doses (1 x 10(2) pfu/mouse) did virus replication occur to levels above the inoculated dose. While light microscopic examination showed classical features of rotavirus infection in the ileum, electron microscopic examination revealed only the accumulation of large numbers of electron-lucent vacuoles in the ileal enterocytes of infected mice. Structures typical of rotavirus morphogenesis were not detected in enterocytes from mice infected with rotavirus SA11.