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Development of an adult mouse model for studies on protection against rotavirus
R L Ward1, M M McNeal, J F Sheridan
1James N. Gamble Institute of Medical Research, Cincinnati, Ohio 45219.
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.
Insights
A new mouse model allows rotavirus infection studies in adult mice, overcoming age limitations. This model demonstrates consistent infection and homotypic protection against rotavirus (EDIM) reinfection.
Area of Science:
- Virology
- Immunology
- Animal Models
Background:
- Rotavirus disease studies in mice are limited by neonatal susceptibility (approx. 15 days).
- Existing models struggle to infect older mice or provide consistent results.
Purpose of the Study:
- To develop an adult mouse model for rotavirus infection studies.
- To overcome the age-related susceptibility limitations in current mouse models.
Main Methods:
- Adapted mouse rotavirus (EDIM) strain using cell culture passages in MA104 cells.
- Oral inoculation of BALB/c mice of various ages (neonatal to 180 days) with adapted EDIM.
- Assessed infection via viral shedding and seroconversion; tested reinfection and heterotypic protection.
Main Results:
- Culture-adapted EDIM consistently infected mice from neonatal to adult stages (up to 180 days old).
- Infected mice showed no reinfection upon subsequent challenge with the same virus.
- Prior infection with EDIM provided homotypic protection but not heterotypic protection against bovine rotavirus.
Conclusions:
- A novel adult mouse model for rotavirus infection was established using cell culture-adapted EDIM.
- This model enables rotavirus research beyond the neonatal period.
- Consistent infection and homotypic immunity were demonstrated, offering insights into rotavirus pathogenesis and immunity.