Development of an adult mouse model for studies on protection against rotavirus

Abstract

Although mice have been used as an animal model for studies on rotavirus disease, these studies have been limited by the short time period after birth during which mice are susceptible to rotavirus illness (i.e., approximately 15 days). To overcome this limitation, an adult mouse model was developed in which the endpoint was infection rather than illness. The model developed utilized a strain of mouse rotavirus (EDIM) adapted to grow in culture by multiple passages in MA104 cells. The second cell culture passage of EDIM caused severe diarrhea in neonatal BALB/c mice, and little or no amelioration of disease was observed after nine cell culture passages, even when this preparation was plaque purified. Oral administration of 2 x 10(3) PFU of passage 9 also consistently caused infection of mice 4, 10, 15, 30, 60, 120, and 180 days of age as determined by viral shedding and seroconversion. Reinoculation of these mice with the same virus preparation at 2, 3, or 4 months after the first inoculation produced no evidence of reinfection. In contrast, infection of neonatal mice with the heterotypic WC3 bovine rotavirus did not prevent reinfection with culture-adapted EDIM. Thus, this strain of EDIM caused consistent infection of previously uninoculated neonatal and adult BALB/c mice and produced homotypic but not heterotypic protection against reinfection.