Skip to main content
Clinical Cardiology logoLink to Clinical Cardiology
. 2009 Feb 3;20(10):857–863. doi: 10.1002/clc.4960201012

Molecular evaluation of enteroviruses in the pathogenesis of idiopathic dilated cardiomyopathy

S Jeffery 1,, P J Kelling 2, A Lukaszyk 2, W J Mckenna 2, Y S Boriskin 3, J C Booth 3, J Hodgson 3, M J Davies 4
PMCID: PMC6655876  PMID: 9377822

Abstract

Background: There is great disparity in the literature as to the presence and relevance of enterovirus in heart tissue from patients with dilated cardiomyopathy (DCM). Published estimates of enteroviral positive tissue in DCM range from 0 to 50%. Very little sequence information is so far available on those samples which are positive.

Hypothesis: Re‐examination of fresh biopsy material from patients previously tested, plus 13 new cases of DCM, and sequencing the products would yield information on the validity of the technique and on the type of virus being detected.

Methods: RNA from biopsy or explant tissue was tested for the presence of enterovirus using reverse transcriptase polymerase chain reaction (PCR). The nucleotide sequences of all positive PCR products were determined by direct sequencing.

Results: Positive PCR signals were found in 10% of samples from patients with DCM and in 16% of control tissues. Two DCM and 12 control samples gave the same nucleotide sequence, which was different from the CB3 used as a positive control. The other 4 DCM samples all produced multiple bands on sequencing.

Conclusion: The results do not support a major role for enterovirus in DCM. There is need for some caution, however, as a review of the literature shows that studies using single biopsies, such as this one, produce consistently lower estimates for enterovirus than do those wherein multiple biopsies are examined.

Keywords: enterovirus, dilated cardiomyopathy, polymerase chain reaction

Full Text

The Full Text of this article is available as a PDF (806.7 KB).

References

  • 1. Archard L, Bowles N, Olsen E, Richardson P: Detection of persistent Coxsackie B virus RNA in dilated cardiomyopathy and myocarditis. Eur Heart J 1987; 8: 437–440 [Google Scholar]
  • 2. Wiegand V, Tracy S, Chapman N, Wucherpfennig C: Enteroviral infection in end stage dilated cardiomyopathy. Klin Wochenschr 1990; 68: 914–920 [DOI] [PubMed] [Google Scholar]
  • 3. Kandolf R: Molecular studies on enteroviral heart disease In New Aspects of Positive Strand RNA Viruses (Eds. Brinton MA, Heinz FX.), p. 340–348. American Society Microbiology, 1990. [Google Scholar]
  • 4. Easton AJ, Eglin RP: The detection of Coxsackievirus RNA in cardiac tissue by in situ hybridisation. J Gen Virol 1988; 69: 285–291 [DOI] [PubMed] [Google Scholar]
  • 5. Tracy S, Chapman NM, McManus BM, Pallansch MA, Beck MA, Carstens J: A molecular and serologic evaluation of enteroviral involvement in human myocarditis. J Mol Cell Cardiol 1990; 22: 403–414 [DOI] [PubMed] [Google Scholar]
  • 6. Jin O, Sole MJ, Butany JW, Cia WK, McLaughlin PR, Lui P, Lie CC: Detection of enterovirus RNA in myocardial biopsies from patients with myocarditis and cardiomyopathy using gene amplification by polymerase chain reaction. Circulation 1990; 82: 8–16 [DOI] [PubMed] [Google Scholar]
  • 7. Keeling PJ, Jeffery S, Caforio ALP, Taylor R, Bottazzo GF, Davies MJ, McKenna WJ: Similar prevalence of enteroviral genome in myocardium from patients with idiopathic dilated cardiomyopathy and controls by the polymerase chain reaction. Br Heart J 1991; 68: 554–559 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8. Muir P, Nicholson F, Jhetam M, Neogi S, Banatvala JE: Rapid diagnosis of enterovirus infection by magnetic bead extraction and polymerase chain reaction detection of enterovirus RNA in clinical specimens. J Clin Micro 1993; 31: 31–38 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9. Weiss LM, Liu XF, Chang KL, Billingham ME: Detection of enteroviral RNA in idiopathic dilated cardiomyopathy and other human cardiac tissues. J Clin Invest 1992; 90: 156–159 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10. Grasso M, Arbustini E, Silini E, Diegoli M, Percivalle E, Ratti G, Bramerio M, Gravazzi AMV, Milanesi G: Search for Coxsackievirus B3 RNA in idiopathic dilated cardiomyopathy using gene amplification by polymerase chain reaction. Am J Cardiol 1992; 69: 658–664 [DOI] [PubMed] [Google Scholar]
  • 11. Liljeqvest JA, Bergstrom T, Holmstrom S, Samuelson A, Yousef GA, Waagstein F, Jeansson S: Failure to demonstrate enterovirus aetiology in Swedish patients with dilated cardiomyopathy. J Gen Virol 1993; 39: 6–10 [DOI] [PubMed] [Google Scholar]
  • 12. Petitjean J, Kopecka H, Freymuth F, Langlard JM, Scanu P, Galateau F, Bouhour JB, Ferriere M, Charbonneau P, Komajda M: Detection of enteroviruses in endomyocardial biopsy by molecular approach. J Med Virol 1992; 37: 76–82 [DOI] [PubMed] [Google Scholar]
  • 13. Giacca M, Severini GM, Mestroni L, Salvi A, Lardieri G, Falaschi A, Camerini F: Low frequency of detection by nested polymerase chain reaction of enterovirus ribonucleic acid in endomyocardial tissue of patients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol 1994; 24: 1033–1040 [DOI] [PubMed] [Google Scholar]
  • 14. Muir P, Nicholson F, Illavia SJ, McNeil TS, Ajetunmobi JF, Dunn H, Starkey WG, Reetoo KN, Cary NRB, Parameshwan J, Banatrala JE: Serological and molecular evidence of enterovirus infection with end‐stage dilated cardiomyopathy. Heart 1996; 76: 243–249 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15. Brandenberg RO, Chazov E, Cherian G, Falase AO, Grosgogeat Y, Kawai C, Loogan F, Judez VM, Orinius E, Goodwin JF, Olsen ECG, Oakley CM, Piza Z: Report of the WHO/ISFC task force on definition and classification of the cardiomyopathies. Circulation 1981; 64: 437A–438A 7196300 [Google Scholar]
  • 16. Manolio TA, Baughman KL, Rodeheffer R, Pearson TA, Bristow D, Michels VV, Abelmann WH, Harlan WR: Prevalence and etiology of idiopathic dilated cardiomyopathy (summary of National Heart, Lung, and Blood Institute workshop). Am J Cardiol 1992; 69: 1458–1466 [DOI] [PubMed] [Google Scholar]
  • 17. Aretz HT, Billingham ME, Edwards WD, Factor FM, Fallon JT, Fenolio JJ, Olsen EG, Schoen FJ: Myocarditis, a histpathologic definition and classification. Am J Cardiovasc Pathol 1987; 1: 3–14 [PubMed] [Google Scholar]
  • 18. Tracy S, Chapman NM, Pistillo JM: Detection of human enteroviruses using the polymerase chain reaction In Frontiers of Virology. Diagnosis of Human Viruses by PCR Technology (Eds. Becker Y, Darai G.), p. 331–344. Heidelberg: Springer‐Verlag, 1992. [Google Scholar]
  • 19. Chapman NM, Tracy S, Gauntt CJ, Fortmueller U: Molecular detection and identification of enterovirus using enzymatic amplification and nucleic acid hybridisation. J Clin Microbiol 1990; 28: 843–850 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20. Chomczynski P, Saachi N: Single step method of RNA isolation by guanidinium thiocyanate‐phenol‐chloroform extraction. Anal Biochem 1987; 162: 156–159 [DOI] [PubMed] [Google Scholar]
  • 21. Feldman AM, Ray P, Silan CM, Mercer JA, Monobe W, Bristow MR: Selective gene amplification in failing human hearts: Quantification of steady state levels of messenger RNA in endomyocardial biopsies using the PCR. Circulation 1991; 83: 1866–1872 [DOI] [PubMed] [Google Scholar]
  • 22. Boriskin Y, Booth JC, Yamada A: Sequence variation within the carboxyl terminus of the nucleoprotein gene of mumps virus strains. Clin Diagn Virol 1994; 2: 79–85 [DOI] [PubMed] [Google Scholar]
  • 23. Sambrook J, Fritsch E, Maniatis T: Molecular cloning. A laboratory manual (2), p. 3–15. New York: Cold Spring Harbor Laboratory Press, 1989. [Google Scholar]
  • 24. Casanova JL, Pannetier C, Jaulin C, Kouilsky P: Optimal conditions for directly sequencing double stranded PCR products with sequenase. Nucl Acids Res 1990; 4028–4032 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25. Bowles NE, Richardson PJ, Olsen EG, Archard LC: Detection of Coxsackie‐B‐virus‐specific RNA sequences in myocardial biopsy samples from patients with myocarditis and dilated cardiomyopathy. Lancet 1986; 1: 1120–1123 [DOI] [PubMed] [Google Scholar]
  • 26. Why HJF, Meany BT, Richardson PJ, Olsen EJ, Bowles NE, Cunningham L, Freek C, Archard LC: Clinical and prognostic significance of detection of enteroviral RNA in the myocardium of patients with myocarditis or dilated cardiomyopathy. Circulation 1994; 89: 2582–2589 [DOI] [PubMed] [Google Scholar]
  • 27. Khan M, Why H, Richardson P, Archard L: Nucleotide sequencing of PCR products shows the presence of Coxsackie B3 virus in endomyocardial biopsies from patients with myocarditis or dilated cardiomyopathy. Biochem Soc Trans 1994; 22: 1765 [DOI] [PubMed] [Google Scholar]
  • 28. Kandolf R, Klingel K, Mertsching H, Canu A, Hohenadl C, Zell R, Reimann BY, Heim A, McManus BM, Foulis AK: Molecular studies on enteroviral heart disease: Patterns of acute and persistent infections. Eur Heart J 1991; 12: 49–55 [DOI] [PubMed] [Google Scholar]
  • 29. Figulla HR, Stille‐Siegener M, Mall G, Heim A, Kreuzer H: Myocardial enterovirus infection with left ventricular dysfunction: A benign disease compared with idiopathic cardiomyopathy. J Am Coll Cardiol 1995; 25: 1170–1175 [DOI] [PubMed] [Google Scholar]
  • 30. Racaniello V: Poliovirus neurovirulence. Adv Virus Res 1988; 34: 217–246 [DOI] [PubMed] [Google Scholar]
  • 31. Tracy S, Chapman NM, Beck M: Molecular biology and pathogenesis of Coxsackie B viruses. Rev Med Virol 1991; 1: 145–154 [Google Scholar]

Articles from Clinical Cardiology are provided here courtesy of Wiley

RESOURCES