Persistence of Enterovirus RNA in Dilated Cardiomyopathy: A Progression from Myocarditis

  • L. C. Archard
  • C. A. Freeke
  • P. J. Richardson
  • B. Meany
  • E. G. J. Olsen
  • P. Morgan-Capner
  • M. L. Rose
  • P. Taylor
  • N. R. Banner
  • M. H. Yacoub
  • N. E. Bowles


We have investigated the role of enterovirus infection in the pathogenesis of myocarditis and dilated cardiomyopathy. In this article we will present evidence (from molecular hybridizations with virus-specific probes) that enteroviruses are major aetiological agents of myocarditis and dilated cardiomyopathy and that virus persistence in myocardium is implicated in the progression from myocarditis to dilated cardiomyopathy.


Dilate Cardiomyopathy Viral Myocarditis Acute Myocarditis Explanted Heart Defective Interfere 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Archard LC, Bowles NE, Olsen EGJ, Richardson PJ (1987) Detection of persistent Coxsackie B virus RNA in dilated cardiomyopathy and myocarditis. Eur Heart J 8 [suppl J]: 437–440Google Scholar
  2. 2.
    Archard LC, Behan PO, Bell EJ, Doyle D, Bowles NE (1988) Postviral fatigue syndrome: persistence of enterovirus RNA in muscle and elevated creatine kinase. J R Soc Med 81: 326–329PubMedGoogle Scholar
  3. 3.
    Arnold DL, Bore PJ, Radda GK, Styles P, Taylor DJ (1984) Excessive intracellular acidosis of skeletal muscle on exercise in a patient with post-viral exhaustion/fatigue syndrome. Lancet 1: 1367–1369PubMedCrossRefGoogle Scholar
  4. 4.
    Baandrup U, Florio RA, Olsen EGJ (1982) Do endomyocardial biopsies represent the morphology of the rest of the myocardium? A quantitative light microscopic study of single v. multiple biopsies with the King’s bioptome. Eur Heart J 3: 171–178PubMedGoogle Scholar
  5. 5.
    Blackburn RV, Righthand F (1987) Viral protein profiles of echovirus 6 recovered from lytic and non-lytic steady state infections. Seventh International Congress of Virology, Edmonton, Canada (Abstr R16.13) 9–14 August 1987Google Scholar
  6. 6.
    Bowles NE, Richardson PJ, Olsen EGJ, Archard LC (1986) Detection of Coxsackie B virus-specific RNA sequences in myocardial biopsy samples from cases of myocarditis and dilated cardiomyopathy. Lancet 1: 1120–1123PubMedCrossRefGoogle Scholar
  7. 7.
    Burch GE, Sun SC, Colclough HL, Sohal S, DePasquale NP (1967) Coxsackie B viral myocarditis and valvulitis in routine autopsy specimens by immunofluorescent techniques. Am Heart J 74: 13–23PubMedCrossRefGoogle Scholar
  8. 8.
    Cambridge G, MacArthur CGC, Waterson AP, Goodwin JF, Oakley CM (1979) Antibodies to Coxsackie B viruses in primary congestive cardiomyopathy. Br Heart J 41: 692–696PubMedCrossRefGoogle Scholar
  9. 9.
    Coltart DJ, El-Hagrassy MMO, Banatvala JE (1984) Coxsackie B virus-specific IgM responses in patients with cardiac and other diseases. In: Bolte HD (ed) Viral heart disease. Springer, Berlin Heidelberg New York, pp 89–94Google Scholar
  10. 10.
    El-Hagrassy MMO, Banatvala JE, Coltart DJ (1980) Coxsackie B virus-specific IgM responses in patients with cardiac and other diseases. Lancet 2: 1160–1162PubMedCrossRefGoogle Scholar
  11. 11.
    Feinberg AP, Vogelstein B (1984) A technique for radiolabelling DNA restriction fragments to high specific activity. Anal Biochem 137: 266–267PubMedCrossRefGoogle Scholar
  12. 12.
    Friedman RM, Ramseur JM (1979) Mechanisms of persistent infections by cytopathic viruses in tissue culture. Arch Virol 60: 83–103PubMedCrossRefGoogle Scholar
  13. 13.
    Godeny EK, Gauntt CJ (1987) In situ immune autoradiographic identification of cells in heart tissues of mice with Coxsackievirus B3-induced myocarditis. Am J Pathol 129: 267–276PubMedGoogle Scholar
  14. 14.
    Goodwin JF (1983) Myocarditis as a possible cause of cardiomyopathy. In: Just H, Schuster HP (eds) Myocarditis — cardiomyopathy. Springer, Berlin Heidelberg New York, pp 7–11Google Scholar
  15. 15.
    Grist NR (1978) Coxsackie virus infections of the heart. In: Waterson AP (ed) Recent advances in clinical virology. Churchill Livingstone, Edingburgh, pp 141–150Google Scholar
  16. 16.
    Grist NR, Bell EJ (1974) A six year study of Coxsackie virus B infections in heart disease. J Hyg 73: 165–172CrossRefGoogle Scholar
  17. 17.
    Hall JL, Dudley L, Dobner PR, Lewis SA, Cowan NJ (1983) Identification of two human beta-tubulin isotypes. Mol Cell Biol 3: 854–862PubMedGoogle Scholar
  18. 18.
    Huber SA, Lodge PA, Job LP (1984) The role of virus-, and immune-mediated cardiocyte injury in Coxsackievirus B3-induced myocarditis. In: Bolte HD (ed) Viral heart disease. Springer, Berlin Heidelberg New York, pp 64–73Google Scholar
  19. 19.
    Iizuka N, Kuge S, Nomoto A (1987) Complete nucleotide sequence of the genome of Coxsackievirus B1. Virology 156: 64–73PubMedCrossRefGoogle Scholar
  20. 20.
    Kaczmarek L, Calabrett B, Baserga R (1985) Expression of cell-cycle-dependent genes in phytohemagglutinin stimulated human lymphocytes. Proc Natl Acad Sci USA 82: 5372–5379CrossRefGoogle Scholar
  21. 21.
    Kandolf R, Hofschneider PH (1985) Molecular cloning of the genome of a cardiotropic Coxsackie B3 virus: full-length reverse-transcribed recombinant cDNA generates infectious virus in mammalian cells. Proc Natl Acad Sci USA 82: 4818–4822PubMedCrossRefGoogle Scholar
  22. 21.a.
    Kandolf R, Canu A, Hofschneider PH (1985) Coxsackie B3 virus can replicate in cultured human foetal heart cells and is inhibited by interferon. J Mol Cell Cardiol 17: 167–181PubMedCrossRefGoogle Scholar
  23. 22.
    King ML, Shaikh A, Bidwell D, Voller A, Banatvala JE (1983) Coxsackie B virus-specific IgM responses in children with insulin-dependent (juvenile-onset; type I) diabetes mellitus. Lancet 1: 1397–1399PubMedCrossRefGoogle Scholar
  24. 23.
    Kuge S, Saito I, Nomoto A (1986) Primary structure of poliovirus defective-interfering particle genomes and possible generation mechanisms of the particles, J Mol Biol 192: 473–487PubMedCrossRefGoogle Scholar
  25. 24.
    Lansdown ABG (1978) Viral infections and diseases of the heart. Prog Med Virol 24: 70–113PubMedGoogle Scholar
  26. 25.
    Lau RCH (1986) Coxsackie B virus-specific IgM responses in coronary care unit patients. J Med Virol 18: 193–198PubMedCrossRefGoogle Scholar
  27. 26.
    Lindberg AM, Stalhandske POK, Pettersson U (1987) Genome of Coxsackievirus B3. Virology 156: 50–63PubMedCrossRefGoogle Scholar
  28. 27.
    MacArthur CGC, Tarin G, Goodwin JF, Hallidie-Smith KA (1984) The relationship of myocarditis to dilated cardiomyopathy. Eur Heart J 5: 1023–1035PubMedGoogle Scholar
  29. 28.
    Maisch B, Deeg P, Liebau G, Kochsiek K (1983) Diagnostic relevance of humoral and cytotoxic immune reactions in primary and secondary dilated cardiomyopathy. Am J Cardiol 52: 1072–1078PubMedCrossRefGoogle Scholar
  30. 29.
    Matteucci D, Paglianti M, Giangregorio AM, Capobianchi MR, Dianzini F, Bendinelli M (1985) Group B Coxsackieviruses readily establish persistent infections in human lymphoid cell lines. J Virol 56: 651–654PubMedGoogle Scholar
  31. 30.
    McCartney RA, Banatvala JE, Bell EJ (1986) Routine use of μ-antibody-capture ELISA for the serological diagnosis of Coxsackie B virus infections. J Med Virol 19: 205–212PubMedCrossRefGoogle Scholar
  32. 31.
    Morgan-Capner P, Richardson PJ, McSorley C, Daly K, Pattison JR (1984) Virus investigations in heart muscle disease. In: Bolte HD (ed) Viral heart disease. Springer, Berlin Heidelberg New York, pp 95–115Google Scholar
  33. 32.
    Olsen EGJ (1979) Pathology of cardiomyopathies. A critical analysis. Am Heart J 98: 385–392PubMedCrossRefGoogle Scholar
  34. 33.
    Olsen EGJ (1985) Histologic aspects of viral myocarditis and its diagnostic criteria. In: Sekiguchi M, Olsen EGJ, Goodwin JF (eds) Myocarditis and related disorders. Springer Berlin Heidelberg New York, pp 130–132Google Scholar
  35. 34.
    Quigley PJ, Richardson PJ, Meany BT, Olsen EGJ, Monaghan MJ, Jackson G, Jewitt JE (1987) Long-term follow-up of acute myocarditis. Correlation of ventricular function and outcome. Eur Heart J 8 (Suppl J): 39–42Google Scholar
  36. 35.
    Reyes MP, Ho K-L, Smith FE, Lerner AM (1981) A mouse model of dilated-type cardiomyopathy due to coxsackievirus B3. J Infect Dis 144: 232–236PubMedCrossRefGoogle Scholar
  37. 36.
    Richardson PJ (1984) Endomyocardial biopsy: technique and evaluation of a new disposable forceps and catheter sheath system. In: Bolte HD (ed) Viral heart disease. Springer, Berlin Heidelberg New York, pp 173–176.Google Scholar
  38. 37.
    Richardson PJ (1985) Clinical aspects of myocarditis. In: Sekiguchi M, Olsen EGJ, Goodwin JF (eds) Myocarditis and related disorders. Springer, Berlin Heidelberg New York, pp 97–100Google Scholar
  39. 38.
    Richardson PJ, Daly K, Gishen P (1984) Haemodynamic findings in biopsy proven acute myocarditis. In: Bolte HD (ed) Viral heart disease. Springer, Berlin Heidelberg New York, pp 165–172Google Scholar
  40. 39.
    Rose ML, Cotes MI, Griffin RJ, Pomerance A, Yacoub MH (1986) Expression of class I and class II major histocompatibility antigens in normal and transplanted human heart. Transplantation 41: 776–780PubMedCrossRefGoogle Scholar
  41. 40.
    Southern P, Oldstone MBA (1986) Medical consequences of persistent viral infection. N Engl J Med 314: 359–367PubMedCrossRefGoogle Scholar
  42. 41.
    Woodruff JF (1980) Viral myocarditis, a review. Am J Pathol 101: 425–484PubMedGoogle Scholar
  43. 42.
    Zhang HY, Yousef GE, Bowles NE, Archard LC, Mann GF, Mowbray JF (1988) Detection of enterovirus RNA in experimentally infected mice by molecular hybridization: specificity of sub-genomic probes in quantitative slot blot and in situ hybridization. J Med Virol (in press)Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1988

Authors and Affiliations

  • L. C. Archard
    • 1
  • C. A. Freeke
    • 1
  • P. J. Richardson
    • 2
  • B. Meany
    • 2
  • E. G. J. Olsen
    • 3
  • P. Morgan-Capner
    • 4
  • M. L. Rose
    • 5
  • P. Taylor
    • 5
  • N. R. Banner
    • 5
  • M. H. Yacoub
    • 5
  • N. E. Bowles
    • 1
  1. 1.Department of BiochemistryCharing Cross and Westminster Medical SchoolLondonUK
  2. 2.Cardiac DepartmentKings College HospitalLondonUK
  3. 3.Histology DepartmentNational Heart HospitalLondonUK
  4. 4.Preston InfirmaryDistrict LaboratoryPrestonUK
  5. 5.Harefield HospitalHarefield, MiddlesexUK

Personalised recommendations