The tyrosine kinase p56lck is essential in coxsackievirus B3-mediated heart disease

Nat Med. 2000 Apr;6(4):429-34. doi: 10.1038/74689.


Infections are thought to be important in the pathogenesis of many heart diseases. Coxsackievirus B3 (CVB3) has been linked to chronic dilated cardiomyopathy, a common cause of progressive heart disease, heart failure and sudden death. We show here that the sarcoma (Src) family kinase Lck (p56lck) is required for efficient CVB3 replication in T-cell lines and for viral replication and persistence in vivo. Whereas infection of wild-type mice with human pathogenic CVB3 caused acute and very severe myocarditis, meningitis, hepatitis, pancreatitis and dilated cardiomyopathy, mice lacking the p56lck gene were completely protected from CVB3-induced acute pathogenicity and chronic heart disease. These data identify a previously unknown function of Src family kinases and indicate that p56lck is the essential host factor that controls the replication and pathogenicity of CVB3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiomyopathy, Dilated / metabolism
  • Cardiomyopathy, Dilated / pathology
  • Cardiomyopathy, Dilated / virology*
  • Chronic Disease
  • Coxsackievirus Infections / metabolism
  • Coxsackievirus Infections / pathology
  • Coxsackievirus Infections / virology*
  • Encephalomyocarditis virus / pathogenicity
  • Enterovirus B, Human / pathogenicity*
  • Enterovirus B, Human / physiology
  • HeLa Cells
  • Humans
  • Jurkat Cells
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / genetics
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / physiology*
  • Mice
  • Mice, Knockout
  • Virus Replication
  • src-Family Kinases / metabolism


  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • src-Family Kinases