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A mouse model of coxsackievirus myocarditis
K R Rozee1, G A Klassen, A Ahmad-Raza
1Department of Microbiology, Victoria General Hospital, Halifax, Nova Scotia.
Objective:
To develop a mouse model of coxsackievirus B3 (CVB3) myocarditis.
Design:
Preliminary studies have indicated that mice infected with CVB3 alone erratically responded with viral myocarditis. Prospective evaluation of the effect of cyclophosphamide at two time intervals resulted in consistency for the development of myocarditis.
Animals:
Juvenile five- to nine-week-old male mice CD-1 type (Charles River Canada Limited).
Interventions:
Infection with coxsackie B3 enterovirus. Pretreatment with cyclophosphamide two days and 4 h before inoculation of 0.2 or 0.15 mg/g. Animals were killed seven, nine, 28 and 63 days post infection.
Main Results:
Following cyclophosphamide conditioning, a tissue response infection with CVB3 was uniformly observed. Virus, however, was infrequently recovered from the myocardium whereas myocarditis became chronic after 28 days.
Conclusions:
Pretreatment of juvenile mice with cyclophosphamide results in a reproducible model of viral myocarditis with chronic changes in the myocardium.
Insights
Developing a reproducible mouse model for coxsackievirus B3 (CVB3) myocarditis is crucial. Cyclophosphamide pretreatment in juvenile mice consistently induces viral myocarditis with chronic cardiac changes.
Area of Science:
- Cardiovascular Research
- Virology
- Immunology
Background:
- Coxsackievirus B3 (CVB3) infection can cause viral myocarditis, but developing a consistent animal model has been challenging.
- Previous studies showed erratic responses in mice infected with CVB3 alone.
Purpose of the Study:
- To establish a reproducible mouse model for studying CVB3-induced myocarditis.
- To investigate the efficacy of cyclophosphamide in inducing consistent myocarditis.
Main Methods:
- Juvenile CD-1 mice were pretreated with cyclophosphamide at two time intervals before CVB3 inoculation.
- Mice were infected with CVB3 and observed for viral myocarditis development.
- Animals were euthanized at 7, 9, 28, and 63 days post-infection for analysis.
Main Results:
- Cyclophosphamide pretreatment uniformly induced a CVB3 infection response in mouse myocardium.
- Myocarditis became chronic, persisting beyond 28 days post-infection.
- Viral recovery from the myocardium was infrequent despite observed myocarditis.
Conclusions:
- Cyclophosphamide pretreatment provides a reproducible method for creating a mouse model of viral myocarditis.
- This model exhibits chronic myocardial changes, valuable for studying CVB3-induced heart disease.