Pancreatic expression of interferon-gamma protects mice from lethal coxsackievirus B3 infection and subsequent myocarditis

Cardiovascular disease is one of the leading causes of death worldwide, and has been associated with many environmental risk factors(1). Recent eviden ce has indicated the involvement of pathogens such as viruses as causative agents, and specifically identified the coxsackievirus B serogroup as the l eading culprit(2,3). Not only has coxsackievirus B3 (CB3) been identified f rom patients with cardiovascular disease(4), but also infection of mice wit h CB3 strains can reproduce human clinical heart disease in rodents(5,6). S everal mechanisms have been proposed in an attempt to distinguish between p athology mediated by direct viral destruction of cardiac muscle cells(7,8) or by the virus-induced immune response directed at infected myocytes(9-11) or at 'mimicked' epitopes shared between viral and cardiac antigens(12-14) . To distinguish between these mechanisms, we infected a unique mouse that diminishes the extent of infection and spread of the virus, but allows comp lete immunity to the virus. Transgenic mice expressing interferon-gamma in their pancreatic beta cells failed to develop CB-3-induced myocarditis. Thi s work challenges the idea of the function of the immune response and 'mole cular mimicry' in the CB-3-induced autoimmune myocarditis model, and instea d favors the idea of virus-mediated damage. These results emphasize the ben efit of reducing the level of viremia early during infection, thereby reduc ing the incidence of virus-mediated heart damage and autoimmunity.