CVB infection and mechanisms of viral cardiomyopathy

Abstract

Coxsackievirus infection has been demonstrated to be a cause of acute and fulminant viral myocarditis and has been associated with dilated cardiomyopathy. While considerable attention has focused on the role of the cellular and humoral, antigen-specific immune system in viral myocarditis, the interaction between the virus and the infected host myocyte is also important. Coxsackievirus has a relative tropism for the heart that is in part mediated by relatively high levels of the coxsackievirus and adenovirus receptor (CAR) on the cardiac myocyte. Once within the myocyte, coxsackievirus produces proteases, such as protease 2A, that have an important role in viral replication, but can also affect host cell proteins such as dystrophin. Cleavage of dystrophin may have a role in release of the virus from the myocyte since viral infection is increased in the absence of dystrophin. In addition to the direct effect of viral proteins on cardiac myocytes, there is now evidence that the cardiac myocyte has a potent innate immune defense against coxsackieviral infection. Suppressors of cytokine signaling (SOCS) can inhibit an interferon-independent mechanism within the cardiac myocyte. In summary, the interaction between coxsackievirus and the infected myocyte has a significant role in the pathogenesis of viral myocarditis and the susceptibility to viral infection.