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

Nat Med. 1999 Mar;5(3):320-6. doi: 10.1038/6543.


Enteroviruses such as Coxsackievirus B3 can cause dilated cardiomyopathy, but the mechanism of this pathology is unknown. Mutations in cytoskeletal proteins such as dystrophin cause hereditary dilated cardiomyopathy, but it is unclear if similar mechanisms underlie acquired forms of heart failure. We demonstrate here that purified Coxsackievirus protease 2A cleaves dystrophin 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 the dystrophin-associated glycoproteins alpha-sarcoglycan and beta-dystroglycan are morphologically disrupted in infected myocytes. We suggest a molecular mechanism through which enteroviral infection contributes to the pathogenesis of acquired forms of dilated cardiomyopathy.

Publication types

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

MeSH terms

  • Animals
  • Cardiomyopathy, Dilated / metabolism*
  • Cardiomyopathy, Dilated / pathology
  • Cells, Cultured
  • Coxsackievirus Infections / metabolism
  • Cysteine Endopeptidases / metabolism*
  • Cytoskeletal Proteins / metabolism*
  • Cytoskeleton / pathology
  • Dystroglycans
  • Dystrophin / metabolism*
  • Enterovirus B, Human / enzymology*
  • Enterovirus B, Human / physiology
  • Humans
  • Male
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred C3H
  • Mice, SCID
  • Myocardium / cytology
  • Rats
  • Sarcolemma / pathology
  • Viral Proteins*


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