CHARACTERIZATION OF A MURINE MODEL OF MYOCARDITIS INDUCED BY A REACTIVATED COXSACKIEVIRUS B3

A transfection-reactivated Coxsackievirus B3 (rCVB3), from a full-leng th cDNA clone of Nancy strain, has previously been shown to be as card iovirulent as the wild-type virus. Myocarditis induced by this genetic ally defined virus was compared in SWR mice with the traditional Balb/ c model. SWR mice inoculated with rCVB3 developed more severe myocardi tis but less severe pancreatitis than Balb/c mice. In contrast to the poor general health and frequent mortality of Balb/c mice following CV B3 infection, the body weight of SWR mice was not affected by CVB3 ino culation and no mortality occurred at titres of 10(2)-10(7) plaque for ming units (PFU). Typical myocarditis developed in SWR mice 7 days pos t infection. Myocarditic foci consisting of necrotic myocardial fibres and mononuclear cell infiltrates resolved by day 30, similar to that observed in Balb/c. However, SWR mice were more sensitive to rCVB3-ind uced myocarditis than were Balb/c mice: mild myocarditis was induced ( 4/4) by as low as 10(2) PFU of the virus (ID50 < 10(1.5) PFU), and mor e severe myocarditis was seen at higher PFU of virus in a dose-depende nt manner. The SWR model was tested with attenuated variants derived f rom cardiovirulent rCVB3. The ID50 for myocarditis was 10(7) PFU for a large plaque-size attenuant and 10(6) PFU for a minute plaque-size at tenuant, indicating loss of cardiovirulence by a factor of more than 1 0(4)-10(5). rCVB3-induced SWR mouse is a sensitive and reliable model for myocarditis. It is useful in assessing the cardiovirulence of diff erent CVB3 variants and evaluating the efficacies of anti-viral therap ies. It will allow follow-up study after high dose infection with card iovirulent rCVB3.