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miRNA as activity markers in Parvo B19 associated heart disease

miRNA als ein Aktivitätsmarker der Parvovirus-B19-assoziierten Herzmuskelerkrankung

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Abstract

Parvovirus B19 is a frequent virus detected in endomyocardial biopsies of patients with clinically suspected myocarditis or dilated cardiomyopathy (DCM). Viruses often cause a more symptomatic disease with increased tissue injury if they become reactivated. A disease-specific differential expression of microRNAs (miRNAs) has been described in the regulation of replicating viruses. Analyzing patients with latent and reactivated B19V infection, we found 29 differentially regulated miRNAs and, in order to test whether predicted genes are differentially expressed, selected mRNAs were tested by TaqMan-QPCR.

Zusammenfassung

Parvovirus B19 ist ein häufiges Virus, das in Endomyokardbiopsien von Patienten mit Verdacht auf Myokarditis oder dilatativer Kardiomyopathie (DCM) nachgewiesen wird. Oft verursachen Viren eine stärker symptomatische Erkrankung mit deutlicherer Gewebeverletzung, wenn sie reaktiviert werden. Eine krankheitsspezifische differenzielle Expression von Mikro-RNAs (miRNAs) wurde in der Regulation der Replikation von Viren beschrieben. Die Analyse von Patienten mit latenter und reaktivierter B19V-Infektion ergab 29 differenziell regulierte miRNAs, und um zu testen, ob vorhergesagte Gene differenziell exprimiert werden, wurden ausgewählte mRNAs mittels TaqMan-qPCR (quantitativer Polymerasekettenreaktion) getestet.

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Abbreviations

ARB:

Angiotensin receptor blocker

B19V:

Erythrovirus/parvovirus B19

DCM:

Dilated cardiomyopathy

EMB:

Endomyocardial biopsy

LVEF:

Left ventricular ejection fraction

LVEDD:

Left ventricular enddiastolic diameter

LVESD:

Left ventricular endsystolic diameter

MI:

Myocardial infarction

PCR:

Polymerase chain reaction

RT-PCR:

Reverse transcription PCR

References

  1. Liu PP, Schultheiss HP (2008) Myocarditis. In: Baunwald (eds) Heart disease. 8. edn. W B Saunders Co, Philadelphia, p 1775–1792

  2. Brown KE, Anderson SM, Young NS (1993) Erythrocyte P antigen: cellular receptor for B19 parvovirus. Science 262(5130):114–117

    Article  PubMed  CAS  Google Scholar 

  3. Weigel-Kelley KA, Yoder MC, Srivastava A (2003) Alpha5beta1 integrin as a cellular coreceptor for human parvovirus B19: requirement of functional activation of beta1 integrin for viral entry. Blood 102:3927–3933

    Article  PubMed  CAS  Google Scholar 

  4. Munakata Y, Saito-Ito T, Kumura-Ishii K et al (2005) Ku80 autoantigen as a cellular coreceptor for human parvovirus B19 infection. Blood 106(10):3449–3458

    Article  PubMed  CAS  Google Scholar 

  5. Bultmann BD, Klingel K, Sotlar K et al (2003) Fatal parvovirus B19-associated myocarditis clinically mimicking ischemic heart disease: an endothelial cell-mediated disease. Hum Pathol 34(1):92–95

    Article  PubMed  Google Scholar 

  6. Klingel K, Sauter M, Bock CT et al (2004) Molecular pathology of inflammatory cardiomyopathy. Med Microbiol Immunol (Berl) 193(2–3):101–107

    Google Scholar 

  7. Bock CT, Klingel K, Aberle S et al (2005) Human parvovirus B19: a new emerging pathogen of inflammatory cardiomyopathy. J Vet Med B Infect Dis Vet Public Health 52:340–343

    Article  PubMed  CAS  Google Scholar 

  8. Bock CT, Klingel K, Kandolf R (2010) Human parvovirus B19-associated myocarditis. N Engl J Med 362(13):1248–1249

    Article  PubMed  CAS  Google Scholar 

  9. Norja P, Hokynar K, Aaltonen LM et al (2006) Bioportfolio: lifelong persistence of variant and prototypic erythrovirus DNA genomes in human tissue. Proc Natl Acad Sci U S A 103(19):7450–7453

    Article  PubMed  CAS  Google Scholar 

  10. Moffat S, Yaegashi N, Tada K et al (1998) Human parvovirus B19 nonstructural (NS1) protein induces apoptosis in erythroid lineage cells. J Virol 72:3018–3028

    Google Scholar 

  11. Hsu TC, Tzang BS, Huang CN et al (2006) Increased expression and secretion of interleukin-6 in human parvovirus B19 non-structural protein (NS1) transfected COS-7 epithelial cells. Clin Exp Immunol 144(1):152–157

    Article  PubMed  CAS  Google Scholar 

  12. Fu Y, Ishii KK, Munakata Y et al (2002) Regulation of tumor necrosis factor alpha promotor by human parvovirus B19 NS1 through activation of AP-1 and AP-2. J Virol 76:5295–5403

    Google Scholar 

  13. Duechting A, Tschope C, Kaiser H et al (2008) Human parvovirus B19 NS1 protein modulates inflammatory signaling by activation of STAT3/PIAS3 in human endothelial cells. J Virol 2008:JVI.00891-08

    Google Scholar 

  14. Poole BD, Karetny YV, Naides S (2004) Parvovirus B19-induced apoptosis of hepatocytes. J Virol 78:7775–7783

    Article  PubMed  CAS  Google Scholar 

  15. Poole BD, Zhou J, Grote A et al (2006) Apoptosis of liver-derived cells induced by parvovirus B19 nonstructural protein. J Virol 80(8):4114–4121

    Article  PubMed  CAS  Google Scholar 

  16. Aretz HT (1987) Myocarditis: the Dallas criteria. Hum Pathol 18(6):619–624

    Article  PubMed  CAS  Google Scholar 

  17. Noutsias M, Seeberg B, Schultheiss HP, Kuhl U (1999) Expression of cell adhesion molecules in dilated cardiomyopathy: evidence for endothelial activation in inflammatory cardiomyopathy. Circulation 99(16):2124–2131

    Article  PubMed  CAS  Google Scholar 

  18. Donoso Mantke O, Nitsche A, Meyer R et al (2004) Analysing myocardial tissue from explanted hearts of heart transplant recipients and multi-organ donors for the presence of parvovirus B19 DNA. J Clin Virol 31(1):32–39

    Article  Google Scholar 

  19. Kuethe F, Lindner J, Matschke K et al (2009) Prevalence of parvovirus B19 and human bocavirus DNA in the heart of patients with no evidence of dilated cardiomyopathy or myocarditis. Clin Infect Dis 49(11):1660–1666

    Article  PubMed  Google Scholar 

  20. Schenk T, Enders M, Pollak S et al (2009) High prevalence of human parvovirus B19 DNA in myocardial autopsy samples from subjects without myocarditis or dilative cardiomyopathy. J Clin Microbiol 47(1):106–110

    Article  PubMed  CAS  Google Scholar 

  21. Tschope C, Bock CT, Kasner M et al (2005) High prevalence of cardiac parvovirus B19 infection in patients with isolated left ventricular diastolic dysfunction. Circulation 111:879–886

    Article  PubMed  CAS  Google Scholar 

  22. Yilmaz A, Mahrholdt H, Athanasiadis A et al (2008) Coronary vasospasm as the underlying cause for chest pain in patients with PVB19 myocarditis. Heart 94(11):1456–1463

    Article  PubMed  CAS  Google Scholar 

  23. Klein RM, Schwartzkopff B, Strauer BE (1998) Evidence of endothelial dysfunction of epicardial coronary arteries in patients with immunohistochemically proven myocarditis. Am Heart J 136(3):389–397

    Article  PubMed  CAS  Google Scholar 

  24. Kühl U, Pauschinger M, Bock T et al (2003) Parvovirus B19 infection mimicking acute myocardial infarction. Circulation 108(8):945–950

    Article  PubMed  Google Scholar 

  25. Vallbracht KB, Schwimmbeck PL, Kuhl U et al (2004) Endothelium-dependent flow-mediated vasodilation of systemic arteries is impaired in patients with myocardial virus persistence. Circulation 110(18):2938–2945

    Article  PubMed  Google Scholar 

  26. Vallbracht KB, Schwimmbeck PL, Kuhl U et al (2005) Differential aspects of endothelial function of the coronary microcirculation considering myocardial virus persistence, endothelial activation, and myocardial leukocyte infiltrates. Circulation 111(14):1784–1791

    Article  PubMed  Google Scholar 

  27. Fischer D, Rossa S, Landmesser U et al (2005) Endothelial dysfunction in patients with chronic heart failure is independently associated with increased incidence of hospitalization, cardiac transplantation, or death. Eur Heart J 26(1):65–69

    Article  PubMed  CAS  Google Scholar 

  28. Lupescu A, Bock C-T, Lang PA et al (2006) Phospholipase A2 activity-dependent stimulation of Ca2+ entry by human parvovirus B19 capsid protein VP1 /JVI.01041–06. J Virol 80(22):11370–11380

    Article  PubMed  CAS  Google Scholar 

  29. Hakeem A, Bhatti S, Fuh A et al (2007) Viral myocarditis masquerading acute coronary syndrome (ACS)–MRI to the rescue. Int J Cardiol 119(3):e74–76

    Article  PubMed  Google Scholar 

  30. Yilmaz A, Kindermann I, Kindermann M et al (2010) Comparative evaluation of left and right ventricular endomyocardial biopsy: differences in complication rate and diagnostic performance. Circulation 122(9):900–909

    Article  PubMed  Google Scholar 

  31. Pozzuto T, Kietzell K von, Bock T et al (2010) Transactivation of human parvovirus B19 gene expression in endothelial cells by adenoviral helper functions. Virology 411(1):50–64

    Article  Google Scholar 

  32. Pellet PE, Ablashi DV, Ambros PF et al (2011) Chromosomally integrated human herpesvirus 6: questions and answers. Rev Med Virol 22:144–155

    Article  Google Scholar 

  33. Cheng JC, Yeh YJ, Tseng CP et al (2012) Let-7B is a novel regulator of hepatitis C virus replication. Cell Mol Life Sci

  34. Munson DJ, Burch AD (2012) A novel miRNA produced during lytic HSV-1 infection is important for efficient replication in tissue culture. Arch Virol

  35. Bae JS, Kim JH, Pasaje CF et al (2012) Association study of genetic variations in microRNAs with the risk of hepatitis B-related liver disease. Dig Liver Dis

  36. Ding X, Ding J, Ning J et al (2012) Circulating microRNA-122 as a potential biomarker for liver injury. Mol Med Report 5(6):1428–1432

    PubMed  CAS  Google Scholar 

  37. Corsten MF, Pagageorgiou A, Verhesen W et al (2012) MicroRNA profiling identifies microRNA-155 as an adverse mediator of cardiac injury and dysfunction during acute viral myocarditis. Circ Res (in press)

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Acknowledgement

This work was supported by grants from the German Research Foundation (DFG), the Transregional Collaborative Research Centre “Inflammatory Cardiomyopathy—Molecular Pathogenesis and Therapy” (SFB TR 19 04) and the Federal Ministry of Education and Research (BMBF, Germany) for the“KMU-innovativ” program (No. 616 0315296). For their excellent technical assistance, we thank Mrs. K. Winter, S. Ochmann, C. Seifert, E. Hertel, M. Willner, and A. Kallel, Berlin, Germany.

Conflicts of interest

On behalf of all authors, the corresponding author states that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Cardiology and Pneumology, Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin, Hindenburgdamm 30, 12200, Berlin, Germany

    U. Kühl M.D., F. Escher & H.-P. Schultheiss

  2. Institut Kardiale Diagnostik und Therapie (IKDT), Berlin, Germany

    M. Rohde, D. Lassner & U.M. Gross

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  1. U. Kühl M.D.
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  2. M. Rohde
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  3. D. Lassner
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  4. U.M. Gross
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  5. F. Escher
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  6. H.-P. Schultheiss
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Correspondence to U. Kühl M.D..

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Kühl, U., Rohde, M., Lassner, D. et al. miRNA as activity markers in Parvo B19 associated heart disease. Herz 37, 637–643 (2012). https://doi.org/10.1007/s00059-012-3656-3

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  • DOI: https://doi.org/10.1007/s00059-012-3656-3

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