Characterization of a murine model of myocarditis induced by a reactivated coxsackievirus B3

Int J Exp Pathol. 1994 Apr;75(2):99-110.


A transfection-reactivated Coxsackievirus B3 (rCVB3), from a full-length cDNA clone of Nancy strain, has previously been shown to be as cardiovirulent as the wild-type virus. Myocarditis induced by this genetically defined virus was compared in SWR mice with the traditional Balb/c model. SWR mice inoculated with rCVB3 developed more severe myocarditis but less severe pancreatitis than Balb/c mice. In contrast to the poor general health and frequent mortality of Balb/c mice following CVB3 infection, the body weight of SWR mice was not affected by CVB3 inoculation and no mortality occurred at titres of 10(2)-10(7) plaque forming units (PFU). Typical myocarditis developed in SWR mice 7 days post 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-induced 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 more severe myocarditis was seen at higher PFU of virus in a dose-dependent manner. The SWR model was tested with attenuated variants derived from 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 attenuant, indicating loss of cardiovirulence by a factor of more than 10(4)-10(5). rCVB3-induced SWR mouse is a sensitive and reliable model for myocarditis. It is useful in assessing the cardiovirulence of different CVB3 variants and evaluating the efficacies of anti-viral therapies. It will allow follow-up study after high dose infection with cardiovirulent rCVB3.

MeSH terms

  • Animals
  • Coxsackievirus Infections / pathology*
  • Disease Models, Animal*
  • Enterovirus B, Human* / isolation & purification
  • Enterovirus B, Human* / pathogenicity
  • Heart / microbiology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred Strains
  • Myocarditis / microbiology*
  • Myocarditis / pathology
  • Myocardium / pathology*
  • Pancreas / pathology
  • Pancreatitis / microbiology
  • Pancreatitis / pathology