Dystrophin disruption in enterovirus-induced myocarditis and dilated cardiomyopathy: from bench to bedside

Med Microbiol Immunol. 2004 May;193(2-3):121-6. doi: 10.1007/s00430-003-0189-7. Epub 2003 Aug 12.


Genetic defects of the dystrophin-glycoprotein complex (DGC) cause hereditary dilated cardiomyopathy. Enteroviruses can also cause cardiomyopathy and we have previously described a mechanism involved in enterovirus-induced dilated cardiomyopathy: The enteroviral protease 2A directly cleaves dystrophin in the hinge 3 region, leading to functional dystrophin impairment. During infection of mice with coxsackievirus B3, the DGC in the heart is disrupted and the sarcolemmal integrity is lost in virus-infected cardiomyocytes. Additionally, dystrophin deficiency markedly increases enterovirus-induced cardiomyopathy in vivo, suggesting a pathogenetic role of the dystrophin cleavage in enterovirus-induced cardiomyopathy. Here, we extend these experimental findings to a patient with dilated cardiomyopathy due to a coxsackievirus B2 myocarditis. Endomyocardial biopsy specimens showed an inflammatory infiltrate and myocytolysis. Immunostaining for the enteroviral capsid antigen VP1 revealed virus-infected cardiomyocytes. Focal areas of cardiomyocytes displayed a loss of the sarcolemmal staining pattern for dystrophin and beta-sarcoglycan identical to previous findings in virus-infected mouse hearts. In vitro, coxsackievirus B2 protease 2A cleaved human dystrophin. These findings demonstrate that in human coxsackievirus B myocarditis a focal disruption of the DGC can principally occur and may contribute to the pathogenesis of human enterovirus-induced dilated cardiomyopathy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Animals
  • Cardiomyopathy, Dilated / pathology*
  • Cardiomyopathy, Dilated / virology
  • Cysteine Endopeptidases / metabolism
  • Cytoskeletal Proteins / metabolism*
  • Dystroglycans
  • Dystrophin / metabolism*
  • Enterovirus B, Human / pathogenicity*
  • Enterovirus Infections / pathology
  • Enterovirus Infections / virology
  • Humans
  • Male
  • Membrane Glycoproteins / metabolism*
  • Myocarditis / pathology*
  • Myocarditis / virology
  • Myocardium / cytology
  • Rabbits
  • Sarcolemma / pathology
  • Viral Proteins*


  • Cytoskeletal Proteins
  • DAG1 protein, human
  • Dystrophin
  • Membrane Glycoproteins
  • Viral Proteins
  • Dystroglycans
  • Cysteine Endopeptidases
  • picornain 2A, Picornavirus