Dilated cardiomyopathy, one of the leading causes of heart failure in the United States, is a multifactorial disease that includes hereditary and acquired forms.1 Although a hereditary component of dilated cardiomyopathy is recognized in 25% to 35%2 of cases, the majority of cases do not have a clearly defined cause. In addition, children and adults can present with an acute onset of cardiomyopathy that is often called acute myocarditis. This is usually attributed to viral infection, although limitations in our diagnostic abilities prevent precise quantitation of the incidence of viral infection in these cases.
Numerous studies have addressed the cellular immune response associated with entero-viral infection; less is known about the interaction between viral proteins and myocyte proteins that contributes to the pathogenesis of enteroviral-mediated cardiomyopathy. This chapter, therefore, focuses on the unique interaction between enteroviral proteins and the cardiac myocyte. This includes a review of murine models of viral-mediated cardio-myopathy, including transgenic mouse experiments that strengthen the evidence for a cause-effect relationship between low-level expression of enteroviral genomes in cardiac myocytes and dilated cardiomyopathy and recent evidence for a role of interferon signaling in the cardiotropic nature of coxsackievirus B3 (CVB3). In addition, evidence is reviewed that demonstrates that an enteroviral protease can directly cleave the myocyte cytoskeletal protein dystrophin, which is known to be important in hereditary dilated cardiomyopathy in humans. Furthermore, the chapter reviews the role that nitric oxide (NO) may play in inactivating this enteroviral protease.
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