Enteroviral protease 2A cleaves dystrophin: Evidence of cytoskeletal disruption in an acquired cardiomyopathy

Enteroviruses such as Coxsackievirus B3 can cause dilated cardiomyopathy, b ut the mechanism of this pathology is unknown. Mutations in cytoskeletal pr oteins such as dystrophin cause hereditary dilated cardiomyopathy, but it i s unclear if similar mechanisms underlie acquired forms of heart failure. W e demonstrate here that purified Coxsackievirus protease 2A cleaves dystrop hin in vitro as predicted by computer analysis. Dystrophin is also cleaved during Coxsackievirus infection of cultured myocytes and in infected mouse hearts, leading to impaired dystrophin function. In vivo, dystrophin and th e dystrophin-associated glycoproteins alpha-sarcoglycan and beta-dystroglyc an are morphologically disrupted in infected myocytes. We suggest a molecul ar mechanism through which enteroviral infection contributes to the pathoge nesis of acquired forms of dilated cardiomyopathy.