Skip to main content
SpringerLink
Log in

Viral Myocarditis

  • Chapter
  • First Online:
Heart Rate and Rhythm

  • 238 Accesses

Abstract

Virus infections are an important factor in the generation of potentially lethal cardiac disease. This chapter describes the viruses most frequently associated with human myocarditis and discusses the mechanisms involved in myocardial infection and pathogenesis. The effects of viral proteases are detrimental to cells by disrupting the integrity of mitochondria, destabilizing the cytoskeleton, impairing Ca2+ homeostasis, and provoking apoptotic processes. Viruses like coxsackievirus B3 may modify cardiac cellular electrophysiology by interacting with vesicular transport of ion channels, leading either to enhanced or to impaired channel protein integration into the plasma membrane. Both, the gain- or loss-of-function can be arrhythmogenic. In addition, viroporins, i.e., viral structures resembling ion channels, also contribute to increased propensity to arrhythmias following viral infection of cardiomyocytes. They conduct Ca2+ and thereby profoundly disrupt cellular Ca2+ homeostasis, induce autophagy, and promote inflammation. Last not least, healing processes lead to fibrosis, the known substrate for re-entry arrhythmias. Amongst the complex immune reactions to viral infection, activation of tumor necrosis factor alpha represents a signaling pathway which for therapeutic interventions with the aim of suppressing arrhythmias associated with viral myocarditis.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 219.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 279.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Disease GBD, Injury I, Prevalence C. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1789–858.

    Article  Google Scholar 

  2. Blauwet LA, Cooper LT. Myocarditis. Prog Cardiovasc Dis. 2010;52(4):274–88.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Bowles NE, Ni J, Kearney DL, Pauschinger M, Schultheiss HP, McCarthy R, et al. Detection of viruses in myocardial tissues by polymerase chain reaction. Evidence of adenovirus as a common cause of myocarditis in children and adults. J Am Coll Cardiol. 2003;42(3):466–72.

    Article  PubMed  Google Scholar 

  4. Grun S, Schumm J, Greulich S, Wagner A, Schneider S, Bruder O, et al. Long-term follow-up of biopsy-proven viral myocarditis: predictors of mortality and incomplete recovery. J Am Coll Cardiol. 2012;59(18):1604–15.

    Article  PubMed  Google Scholar 

  5. Maisch B, Alter P. Treatment options in myocarditis and inflammatory cardiomyopathy : focus on i.v. immunoglobulins. Herz. 2018;43(5):423–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Pankuweit S, Moll R, Baandrup U, Portig I, Hufnagel G, Maisch B. Prevalence of the parvovirus B19 genome in endomyocardial biopsy specimens. Hum Pathol. 2003;34(5):497–503.

    Article  PubMed  Google Scholar 

  7. Kuhl U, Pauschinger M, Seeberg B, Lassner D, Noutsias M, Poller W, et al. Viral persistence in the myocardium is associated with progressive cardiac dysfunction. Circulation. 2005;112(13):1965–70.

    Article  PubMed  Google Scholar 

  8. Mahrholdt H, Wagner A, Deluigi CC, Kispert E, Hager S, Meinhardt G, et al. Presentation, patterns of myocardial damage, and clinical course of viral myocarditis. Circulation. 2006;114(15):1581–90.

    Article  PubMed  Google Scholar 

  9. Caforio AL, Calabrese F, Angelini A, Tona F, Vinci A, Bottaro S, et al. A prospective study of biopsy-proven myocarditis: prognostic relevance of clinical and aetiopathogenetic features at diagnosis. Eur Heart J. 2007;28(11):1326–33.

    Article  PubMed  Google Scholar 

  10. Kindermann I, Kindermann M, Kandolf R, Klingel K, Bultmann B, Muller T, et al. Predictors of outcome in patients with suspected myocarditis. Circulation. 2008;118(6):639–48.

    Article  PubMed  Google Scholar 

  11. Nielsen TS, Hansen J, Nielsen LP, Baandrup UT, Banner J. The presence of enterovirus, adenovirus, and parvovirus B19 in myocardial tissue samples from autopsies: an evaluation of their frequencies in deceased individuals with myocarditis and in non-inflamed control hearts. Forensic Sci Med Pathol. 2014;10(3):344–50.

    Article  CAS  PubMed  Google Scholar 

  12. Verdonschot J, Hazebroek M, Merken J, Debing Y, Dennert R, Brunner-La Rocca HP, et al. Relevance of cardiac parvovirus B19 in myocarditis and dilated cardiomyopathy: review of the literature. Eur J Heart Fail. 2016;18(12):1430–41.

    Article  PubMed  Google Scholar 

  13. Magnani JW, Dec GW. Myocarditis: current trends in diagnosis and treatment. Circulation. 2006;113(6):876–90.

    Article  PubMed  Google Scholar 

  14. Yajima T, Knowlton KU. Viral myocarditis: from the perspective of the virus. Circulation. 2009;119(19):2615–24.

    Article  PubMed  Google Scholar 

  15. Leung HS, Li OT, Chan RW, Chan MC, Nicholls JM, Poon LL. Entry of influenza a virus with a alpha2,6-linked sialic acid binding preference requires host fibronectin. J Virol. 2012;86(19):10704–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Woodruff JF. Viral myocarditis. A review. Am J Pathol. 1980;101(2):425–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Coyne CB, Bergelson JM. Virus-induced Abl and Fyn kinase signals permit coxsackievirus entry through epithelial tight junctions. Cell. 2006;124(1):119–31.

    Article  CAS  PubMed  Google Scholar 

  18. Li T, Chen X, Garbutt KC, Zhou P, Zheng N. Structure of DDB1 in complex with a paramyxovirus V protein: viral hijack of a propeller cluster in ubiquitin ligase. Cell. 2006;124(1):105–17.

    Article  CAS  PubMed  Google Scholar 

  19. Marchant D, Sall A, Si X, Abraham T, Wu W, Luo Z, et al. ERK MAP kinase-activated Arf6 trafficking directs coxsackievirus type B3 into an unproductive compartment during virus host-cell entry. J Gen Virol. 2009;90(Pt 4):854–62.

    Article  CAS  PubMed  Google Scholar 

  20. Albecka A, Laine RF, Janssen AF, Kaminski CF, Crump CM. HSV-1 glycoproteins are delivered to virus assembly sites through dynamin-dependent endocytosis. Traffic. 2016;17(1):21–39.

    Article  CAS  PubMed  Google Scholar 

  21. Babe LM, Craik CS. Viral proteases: evolution of diverse structural motifs to optimize function. Cell. 1997;91(4):427–30.

    Article  CAS  PubMed  Google Scholar 

  22. Peischard S, Ho HT, Theiss C, Strutz-Seebohm N, Seebohm G. A kidnapping story: how Coxsackievirus B3 and its host cell interact. Cell Physiol Biochem. 2019;53(1):121–40.

    Article  CAS  PubMed  Google Scholar 

  23. Lewis SM, Cerquozzi S, Graber TE, Ungureanu NH, Andrews M, Holcik M. The eIF4G homolog DAP5/p97 supports the translation of select mRNAs during endoplasmic reticulum stress. Nucleic Acids Res. 2008;36(1):168–78.

    Article  CAS  PubMed  Google Scholar 

  24. Chau DH, Yuan J, Zhang H, Cheung P, Lim T, Liu Z, et al. Coxsackievirus B3 proteases 2A and 3C induce apoptotic cell death through mitochondrial injury and cleavage of eIF4GI but not DAP5/p97/NAT1. Apoptosis. 2007;12(3):513–24.

    Article  CAS  PubMed  Google Scholar 

  25. Hanson PJ, Ye X, Qiu Y, Zhang HM, Hemida MG, Wang F, et al. Cleavage of DAP5 by coxsackievirus B3 2A protease facilitates viral replication and enhances apoptosis by altering translation of IRES-containing genes. Cell Death Differ. 2016;23(5):828–40.

    Article  CAS  PubMed  Google Scholar 

  26. Joo CH, Hong HN, Kim EO, Im JO, Yoon SY, Ye JS, et al. Coxsackievirus B3 induces apoptosis in the early phase of murine myocarditis: a comparative analysis of cardiovirulent and noncardiovirulent strains. Intervirology. 2003;46(3):135–40.

    Article  PubMed  Google Scholar 

  27. Cai Z, Shen L, Ma H, Yang J, Yang D, Chen H, et al. Involvement of endoplasmic reticulum stress-mediated C/EBP homologous protein activation in Coxsackievirus B3-induced acute viral myocarditis. Circ Heart Fail. 2015;8(4):809–18.

    Article  CAS  PubMed  Google Scholar 

  28. Lin L, Zhang M, Yan R, Shan H, Diao J, Wei J. Inhibition of Drp1 attenuates mitochondrial damage and myocardial injury in Coxsackievirus B3 induced myocarditis. Biochem Biophys Res Commun. 2017;484(3):550–6.

    Article  CAS  PubMed  Google Scholar 

  29. Lackner LL, Nunnari J. Small molecule inhibitors of mitochondrial division: tools that translate basic biological research into medicine. Chem Biol. 2010;17(6):578–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ebermann L, Wika S, Klumpe I, Hammer E, Klingel K, Lassner D, et al. The mitochondrial respiratory chain has a critical role in the antiviral process in Coxsackievirus B3-induced myocarditis. Lab Investig. 2012;92(1):125–34.

    Article  CAS  PubMed  Google Scholar 

  31. Xie B, Zhou JF, Lu Q, Li CJ, Chen P. Oxidative stress in patients with acute coxsackie virus myocarditis. Biomed Environ Sci. 2002;15(1):48–57.

    PubMed  Google Scholar 

  32. Badorff C, Fichtlscherer B, Rhoads RE, Zeiher AM, Muelsch A, Dimmeler S, et al. Nitric oxide inhibits dystrophin proteolysis by coxsackieviral protease 2A through S-nitrosylation: a protective mechanism against enteroviral cardiomyopathy. Circulation. 2000;102(18):2276–81.

    Article  CAS  PubMed  Google Scholar 

  33. Mavrogeni S, Papavasiliou A, Spargias K, Constandoulakis P, Papadopoulos G, Karanasios E, et al. Myocardial inflammation in Duchenne muscular dystrophy as a precipitating factor for heart failure: a prospective study. BMC Neurol. 2010;10:33.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Badorff C, Lee GH, Lamphear BJ, Martone ME, Campbell KP, Rhoads RE, et al. Enteroviral protease 2A cleaves dystrophin: evidence of cytoskeletal disruption in an acquired cardiomyopathy. Nat Med. 1999;5(3):320–6.

    Article  CAS  PubMed  Google Scholar 

  35. Cranefield PF, Wit AL. Cardiac arrhythmias. Annu Rev Physiol. 1979;41:459–72.

    Article  CAS  PubMed  Google Scholar 

  36. Priest BT, McDermott JS. Cardiac ion channels. Channels (Austin). 2015;9(6):352–9.

    Article  PubMed  Google Scholar 

  37. Seebohm G, Strutz-Seebohm N, Ureche ON, Henrion U, Baltaev R, Mack AF, et al. Long QT syndrome-associated mutations in KCNQ1 and KCNE1 subunits disrupt normal endosomal recycling of IKs channels. Circ Res. 2008;103(12):1451–7.

    Article  CAS  PubMed  Google Scholar 

  38. Steinke K, Sachse F, Ettischer N, Strutz-Seebohm N, Henrion U, Rohrbeck M, et al. Coxsackievirus B3 modulates cardiac ion channels. FASEB J. 2013;27(10):4108–21.

    Article  CAS  PubMed  Google Scholar 

  39. Kaese S, Larbig R, Rohrbeck M, Frommeyer G, Dechering D, Olligs J, et al. Electrophysiological alterations in a murine model of chronic coxsackievirus B3 myocarditis. PLoS One. 2017;12(6):e0180029.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Melton JV, Ewart GD, Weir RC, Board PG, Lee E, Gage PW. Alphavirus 6K proteins form ion channels. J Biol Chem. 2002;277(49):46923–31.

    Article  CAS  PubMed  Google Scholar 

  41. Ewart GD, Sutherland T, Gage PW, Cox GB. The Vpu protein of human immunodeficiency virus type 1 forms cation-selective ion channels. J Virol. 1996;70(10):7108–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Hyser JM, Estes MK. Pathophysiological consequences of calcium-conducting viroporins. Annu Rev Virol. 2015;2(1):473–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Nieva JL, Madan V, Carrasco L. Viroporins: structure and biological functions. Nat Rev Microbiol. 2012;10(8):563–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Giorda KM, Hebert DN. Viroporins customize host cells for efficient viral propagation. DNA Cell Biol. 2013;32(10):557–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. van Kuppeveld FJ, Hoenderop JG, Smeets RL, Willems PH, Dijkman HB, Galama JM, et al. Coxsackievirus protein 2B modifies endoplasmic reticulum membrane and plasma membrane permeability and facilitates virus release. EMBO J. 1997;16(12):3519–32.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Dennert R, Crijns HJ, Heymans S. Acute viral myocarditis. Eur Heart J. 2008;29(17):2073–82.

    Article  PubMed  PubMed Central  Google Scholar 

  47. van Kuppeveld FJ, Galama JM, Zoll J, Melchers WJ. Genetic analysis of a hydrophobic domain of coxsackie B3 virus protein 2B: a moderate degree of hydrophobicity is required for a cis-acting function in viral RNA synthesis. J Virol. 1995;69(12):7782–90.

    Article  PubMed  PubMed Central  Google Scholar 

  48. van Kuppeveld FJ, Galama JM, Zoll J, van den Hurk PJ, Melchers WJ. Coxsackie B3 virus protein 2B contains cationic amphipathic helix that is required for viral RNA replication. J Virol. 1996;70(6):3876–86.

    Article  PubMed  PubMed Central  Google Scholar 

  49. van Kuppeveld FJ, van den Hurk PJ, Zoll J, Galama JM, Melchers WJ. Mutagenesis of the coxsackie B3 virus 2B/2C cleavage site: determinants of processing efficiency and effects on viral replication. J Virol. 1996;70(11):7632–40.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Sanchez-Martinez S, Madan V, Carrasco L, Nieva JL. Membrane-active peptides derived from picornavirus 2B viroporin. Curr Protein Pept Sci. 2012;13(7):632–43.

    Article  CAS  PubMed  Google Scholar 

  51. de Jong AS, de Mattia F, Van Dommelen MM, Lanke K, Melchers WJ, Willems PH, et al. Functional analysis of picornavirus 2B proteins: effects on calcium homeostasis and intracellular protein trafficking. J Virol. 2008;82(7):3782–90.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Campanella M, de Jong AS, Lanke KW, Melchers WJ, Willems PH, Pinton P, et al. The coxsackievirus 2B protein suppresses apoptotic host cell responses by manipulating intracellular Ca2+ homeostasis. J Biol Chem. 2004;279(18):18440–50.

    Article  CAS  PubMed  Google Scholar 

  53. Putney JW Jr. A model for receptor-regulated calcium entry. Cell Calcium. 1986;7(1):1–12.

    Article  CAS  PubMed  Google Scholar 

  54. Putney JW Jr. Store-operated calcium channels: how do we measure them, and why do we care? Sci STKE. 2004;2004(243):pe37.

    Article  PubMed  Google Scholar 

  55. Zhou Y, Frey TK, Yang JJ. Viral calciomics: interplays between Ca2+ and virus. Cell Calcium. 2009;46(1):1–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Li Z, Zou Z, Jiang Z, Huang X, Liu Q. Biological function and application of picornaviral 2B protein: a new target for antiviral drug development. Viruses. 2019;11(6):510.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Ow YP, Green DR, Hao Z, Mak TW. Cytochrome c: functions beyond respiration. Nat Rev Mol Cell Biol. 2008;9(7):532–42.

    Article  CAS  PubMed  Google Scholar 

  58. Carthy CM, Yanagawa B, Luo H, Granville DJ, Yang D, Cheung P, et al. Bcl-2 and Bcl-xL overexpression inhibits cytochrome c release, activation of multiple caspases, and virus release following coxsackievirus B3 infection. Virology. 2003;313(1):147–57.

    Article  CAS  PubMed  Google Scholar 

  59. Carthy CM, Granville DJ, Watson KA, Anderson DR, Wilson JE, Yang D, et al. Caspase activation and specific cleavage of substrates after coxsackievirus B3-induced cytopathic effect in HeLa cells. J Virol. 1998;72(9):7669–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Paloheimo O, Ihalainen TO, Tauriainen S, Valilehto O, Kirjavainen S, Niskanen EA, et al. Coxsackievirus B3-induced cellular protrusions: structural characteristics and functional competence. J Virol. 2011;85(13):6714–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Fung TS, Torres J, Liu DX. The emerging roles of viroporins in ER stress response and autophagy induction during virus infection. Viruses. 2015;7(6):2834–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Wong J, Zhang J, Si X, Gao G, Mao I, McManus BM, et al. Autophagosome supports coxsackievirus B3 replication in host cells. J Virol. 2008;82(18):9143–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Zhai X, Bai B, Yu B, Wang T, Wang H, Wang Y, et al. Coxsackievirus B3 induces Autophagic response in cardiac myocytes in vivo. Biochemistry (Mosc). 2015;80(8):1001–9.

    Article  CAS  PubMed  Google Scholar 

  64. Wu H, Zhai X, Chen Y, Wang R, Lin L, Chen S, et al. Protein 2B of Coxsackievirus B3 induces autophagy relying on its transmembrane hydrophobic sequences. Viruses. 2016;8(5):131.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Crawford SE, Hyser JM, Utama B, Estes MK. Autophagy hijacked through viroporin-activated calcium/calmodulin-dependent kinase kinase-beta signaling is required for rotavirus replication. Proc Natl Acad Sci U S A. 2012;109(50):E3405–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Taylor MP, Kirkegaard K. Modification of cellular autophagy protein LC3 by poliovirus. J Virol. 2007;81(22):12543–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Broz P, Dixit VM. Inflammasomes: mechanism of assembly, regulation and signalling. Nat Rev Immunol. 2016;16(7):407–20.

    Article  CAS  PubMed  Google Scholar 

  68. Wang Y, Gao B, Xiong S. Involvement of NLRP3 inflammasome in CVB3-induced viral myocarditis. Am J Physiol Heart Circ Physiol. 2014;307(10):H1438–47.

    Article  CAS  PubMed  Google Scholar 

  69. Tschopp J, Schroder K. NLRP3 inflammasome activation: the convergence of multiple signalling pathways on ROS production? Nat Rev Immunol. 2010;10(3):210–5.

    Article  CAS  PubMed  Google Scholar 

  70. Ito M, Yanagi Y, Ichinohe T. Encephalomyocarditis virus viroporin 2B activates NLRP3 inflammasome. PLoS Pathog. 2012;8(8):e1002857.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Triantafilou K, Kar S, van Kuppeveld FJ, Triantafilou M. Rhinovirus-induced calcium flux triggers NLRP3 and NLRC5 activation in bronchial cells. Am J Respir Cell Mol Biol. 2013;49(6):923–34.

    Article  CAS  PubMed  Google Scholar 

  72. Cornell CT, Kiosses WB, Harkins S, Whitton JL. Inhibition of protein trafficking by coxsackievirus b3: multiple viral proteins target a single organelle. J Virol. 2006;80(13):6637–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Fabiato A. Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum. Am J Phys. 1983;245(1):C1–14.

    Article  CAS  Google Scholar 

  74. Bers DM. Cardiac excitation-contraction coupling. Nature. 2002;415(6868):198–205.

    Article  CAS  PubMed  Google Scholar 

  75. Zhang A, Zhang H, Wu S. Immunomodulation by atorvastatin upregulates expression of gap junction proteins in coxsackievirus B3 (CVB3)-induced myocarditis. Inflamm Res. 2010;59(4):255–62.

    Article  CAS  PubMed  Google Scholar 

  76. Lozano MD, Rubocki RJ, Wilson JE, McManus BM, Wisecarver JL. Human leukocyte antigen class II associations in patients with idiopathic dilated cardiomyopathy. Myocarditis Treatment Trial Investigators. J Card Fail. 1997;3(2):97–103.

    Article  CAS  PubMed  Google Scholar 

  77. Tchilian EZ, Gil J, Navarro ML, Fernandez-Cruz E, Chapel H, Misbah S, et al. Unusual case presentations associated with the CD45 C77G polymorphism. Clin Exp Immunol. 2006;146(3):448–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Aderem A, Ulevitch RJ. Toll-like receptors in the induction of the innate immune response. Nature. 2000;406(6797):782–7.

    Article  CAS  PubMed  Google Scholar 

  79. Ong S, Rose NR, Cihakova D. Natural killer cells in inflammatory heart disease. Clin Immunol. 2017;175:26–33.

    Article  CAS  PubMed  Google Scholar 

  80. Karupiah G, Xie QW, Buller RM, Nathan C, Duarte C, MacMicking JD. Inhibition of viral replication by interferon-gamma-induced nitric oxide synthase. Science. 1993;261(5127):1445–8.

    Article  CAS  PubMed  Google Scholar 

  81. Matsumori A, Tomioka N, Kawai C. Protective effect of recombinant alpha interferon on coxsackievirus B3 myocarditis in mice. Am Heart J. 1988;115(6):1229–32.

    Article  CAS  PubMed  Google Scholar 

  82. Wang YX, da Cunha V, Vincelette J, White K, Velichko S, Xu Y, et al. Antiviral and myocyte protective effects of murine interferon-beta and -{alpha}2 in coxsackievirus B3-induced myocarditis and epicarditis in Balb/c mice. Am J Physiol Heart Circ Physiol. 2007;293(1):H69–76.

    Article  CAS  PubMed  Google Scholar 

  83. Medzhitov R, Preston-Hurlburt P, Janeway CA Jr. A human homologue of the drosophila toll protein signals activation of adaptive immunity. Nature. 1997;388(6640):394–7.

    Article  CAS  PubMed  Google Scholar 

  84. Kawano Y, Noma T, Kou K, Yoshizawa I, Yata J. Regulation of human IgG subclass production by cytokines: human IgG subclass production enhanced differentially by interleukin-6. Immunology. 1995;84(2):278–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Arango Duque G, Descoteaux A. Macrophage cytokines: involvement in immunity and infectious diseases. Front Immunol. 2014;5:491.

    Article  PubMed  PubMed Central  Google Scholar 

  86. Takeda K, Akira S. Toll-like receptors in innate immunity. Int Immunol. 2005;17(1):1–14.

    Article  CAS  PubMed  Google Scholar 

  87. Uematsu S, Akira S. Toll-like receptors (TLRs) and their ligands. Handb Exp Pharmacol. 2008;183:1–20.

    Article  CAS  Google Scholar 

  88. Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, et al. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol. 2004;5(7):730–7.

    Article  CAS  PubMed  Google Scholar 

  89. Yoneyama M, Kikuchi M, Matsumoto K, Imaizumi T, Miyagishi M, Taira K, et al. Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. J Immunol. 2005;175(5):2851–8.

    Article  CAS  PubMed  Google Scholar 

  90. Hiscott J, Lin R, Nakhaei P, Paz S. MasterCARD: a priceless link to innate immunity. Trends Mol Med. 2006;12(2):53–6.

    Article  CAS  PubMed  Google Scholar 

  91. Yasukawa H, Yajima T, Duplain H, Iwatate M, Kido M, Hoshijima M, et al. The suppressor of cytokine signaling-1 (SOCS1) is a novel therapeutic target for enterovirus-induced cardiac injury. J Clin Invest. 2003;111(4):469–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Yajima T, Yasukawa H, Jeon ES, Xiong D, Dorner A, Iwatate M, et al. Innate defense mechanism against virus infection within the cardiac myocyte requiring gp130-STAT3 signaling. Circulation. 2006;114(22):2364–73.

    Article  CAS  PubMed  Google Scholar 

  93. Sivasubramanian N, Coker ML, Kurrelmeyer KM, MacLellan WR, DeMayo FJ, Spinale FG, et al. Left ventricular remodeling in transgenic mice with cardiac restricted overexpression of tumor necrosis factor. Circulation. 2001;104(7):826–31.

    Article  CAS  PubMed  Google Scholar 

  94. Hodgson DM, Zingman LV, Kane GC, Perez-Terzic C, Bienengraeber M, Ozcan C, et al. Cellular remodeling in heart failure disrupts K(ATP) channel-dependent stress tolerance. EMBO J. 2003;22(8):1732–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Chung ES, Packer M, Lo KH, Fasanmade AA, Willerson JT, Anti TNFTACHFI. Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF therapy against congestive heart failure (ATTACH) trial. Circulation. 2003;107(25):3133–40.

    Article  CAS  PubMed  Google Scholar 

  96. Norja P, Hokynar K, Aaltonen LM, Chen R, Ranki A, Partio EK, et al. Bioportfolio: lifelong persistence of variant and prototypic erythrovirus DNA genomes in human tissue. Proc Natl Acad Sci U S A. 2006;103(19):7450–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Kuhl U, Lassner D, von Schlippenbach J, Poller W, Schultheiss HP. Interferon-Beta improves survival in enterovirus-associated cardiomyopathy. J Am Coll Cardiol. 2012;60(14):1295–6.

    Article  PubMed  Google Scholar 

  98. Kuhl U, Lassner D, Dorner A, Rohde M, Escher F, Seeberg B, et al. A distinct subgroup of cardiomyopathy patients characterized by transcriptionally active cardiotropic erythrovirus and altered cardiac gene expression. Basic Res Cardiol. 2013;108(5):372.

    Article  CAS  PubMed  Google Scholar 

  99. Pellett PE, Ablashi DV, Ambros PF, Agut H, Caserta MT, Descamps V, et al. Chromosomally integrated human herpesvirus 6: questions and answers. Rev Med Virol. 2012;22(3):144–55.

    Article  CAS  PubMed  Google Scholar 

  100. Escher F, Kuhl U, Gross U, Westermann D, Poller W, Tschope C, et al. Aggravation of left ventricular dysfunction in patients with biopsy-proven cardiac human herpesvirus A and B infection. J Clin Virol. 2015;63:1–5.

    Article  CAS  PubMed  Google Scholar 

  101. Kaya Z, Leib C, Katus HA. Autoantibodies in heart failure and cardiac dysfunction. Circ Res. 2012;110(1):145–58.

    Article  CAS  PubMed  Google Scholar 

  102. Lazzerini PE, Capecchi PL, Laghi-Pasini F, Boutjdir M. Autoimmune channelopathies as a novel mechanism in cardiac arrhythmias. Nat Rev Cardiol. 2017;14(9):521–35.

    Article  CAS  PubMed  Google Scholar 

  103. Kaya Z, Katus HA, Rose NR. Cardiac troponins and autoimmunity: their role in the pathogenesis of myocarditis and of heart failure. Clin Immunol. 2010;134(1):80–8.

    Article  CAS  PubMed  Google Scholar 

  104. Dominguez F, Kuhl U, Pieske B, Garcia-Pavia P, Tschope C. Update on myocarditis and inflammatory cardiomyopathy: reemergence of endomyocardial biopsy. Rev Esp Cardiol (Engl Ed). 2016;69(2):178–87.

    Article  PubMed  Google Scholar 

  105. Muckelbauer JK, Kremer M, Minor I, Diana G, Dutko FJ, Groarke J, et al. The structure of coxsackievirus B3 at 3.5 a resolution. Structure. 1995;3(7):653–67.

    Article  CAS  PubMed  Google Scholar 

  106. Andreoletti L, Leveque N, Boulagnon C, Brasselet C, Fornes P. Viral causes of human myocarditis. Arch Cardiovasc Dis. 2009;102(6–7):559–68.

    Article  PubMed  Google Scholar 

  107. Rombaut B, Vrijsen R, Boeye A. Comparison of arildone and 3-methylquercetin as stabilizers of poliovirus. Antiviral Res. 1985;1(Suppl 1):67–73.

    Article  Google Scholar 

  108. Pevear DC, Fancher MJ, Felock PJ, Rossmann MG, Miller MS, Diana G, et al. Conformational change in the floor of the human rhinovirus canyon blocks adsorption to HeLa cell receptors. J Virol. 1989;63(5):2002–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Cohen S, Au S, Pante N. How viruses access the nucleus. Biochim Biophys Acta. 2011;1813(9):1634–45.

    Article  CAS  PubMed  Google Scholar 

  110. Wang T, Yu B, Lin L, Zhai X, Han Y, Qin Y, et al. A functional nuclear localization sequence in the VP1 capsid protein of coxsackievirus B3. Virology. 2012;433(2):513–21.

    Article  CAS  PubMed  Google Scholar 

  111. Abaitua F, Hollinshead M, Bolstad M, Crump CM, O'Hare P. A nuclear localization signal in herpesvirus protein VP1-2 is essential for infection via capsid routing to the nuclear pore. J Virol. 2012;86(17):8998–9014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Wang Y, Zhao S, Chen Y, Wang T, Dong C, Wo X, et al. The capsid protein VP1 of Coxsackievirus B induces cell cycle arrest by up-regulating heat shock protein 70. Front Microbiol. 2019;10:1633.

    Article  PubMed  PubMed Central  Google Scholar 

  113. Knowlton KU, Jeon ES, Berkley N, Wessely R, Huber S. A mutation in the puff region of VP2 attenuates the myocarditic phenotype of an infectious cDNA of the Woodruff variant of coxsackievirus B3. J Virol. 1996;70(11):7811–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Stadnick E, Dan M, Sadeghi A, Chantler JK. Attenuating mutations in coxsackievirus B3 map to a conformational epitope that comprises the puff region of VP2 and the knob of VP3. J Virol. 2004;78(24):13987–4002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Henke A, Launhardt H, Klement K, Stelzner A, Zell R, Munder T. Apoptosis in coxsackievirus B3-caused diseases: interaction between the capsid protein VP2 and the proapoptotic protein siva. J Virol. 2000;74(9):4284–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Chehadeh W, Lobert PE, Sauter P, Goffard A, Lucas B, Weill J, et al. Viral protein VP4 is a target of human antibodies enhancing coxsackievirus B4- and B3-induced synthesis of alpha interferon. J Virol. 2005;79(22):13882–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Ramsingh AI, Collins DN. A point mutation in the VP4 coding sequence of coxsackievirus B4 influences virulence. J Virol. 1995;69(11):7278–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. McCarthy RE 3rd, Boehmer JP, Hruban RH, Hutchins GM, Kasper EK, Hare JM, et al. Long-term outcome of fulminant myocarditis as compared with acute (nonfulminant) myocarditis. N Engl J Med. 2000;342(10):690–5.

    Article  PubMed  Google Scholar 

  119. Lieberman EB, Hutchins GM, Herskowitz A, Rose NR, Baughman KL. Clinicopathologic description of myocarditis. J Am Coll Cardiol. 1991;18(7):1617–26.

    Article  CAS  PubMed  Google Scholar 

  120. Burke AP, Saenger J, Mullick F, Virmani R. Hypersensitivity myocarditis. Arch Pathol Lab Med. 1991;115(8):764–9.

    CAS  PubMed  Google Scholar 

  121. Getz MA, Subramanian R, Logemann T, Ballantyne F. Acute necrotizing eosinophilic myocarditis as a manifestation of severe hypersensitivity myocarditis. Antemortem diagnosis and successful treatment. Ann Intern Med. 1991;115(3):201–2.

    Article  CAS  PubMed  Google Scholar 

  122. Galiuto L, Enriquez-Sarano M, Reeder GS, Tazelaar HD, Li JT, Miller FA Jr, et al. Eosinophilic myocarditis manifesting as myocardial infarction: early diagnosis and successful treatment. Mayo Clin Proc. 1997;72(7):603–10.

    Article  CAS  PubMed  Google Scholar 

  123. Cooper LT Jr, Berry GJ, Shabetai R. Idiopathic giant-cell myocarditis--natural history and treatment. Multicenter Giant Cell Myocarditis Study Group Investigators. N Engl J Med. 1997;336(26):1860–6.

    Article  PubMed  Google Scholar 

  124. Menghini VV, Savcenko V, Olson LJ, Tazelaar HD, Dec GW, Kao A, et al. Combined immunosuppression for the treatment of idiopathic giant cell myocarditis. Mayo Clin Proc. 1999;74(12):1221–6.

    Article  CAS  PubMed  Google Scholar 

  125. Aretz HT. Myocarditis: the Dallas criteria. Hum Pathol. 1987;18(6):619–24.

    Article  CAS  PubMed  Google Scholar 

  126. Martin AB, Webber S, Fricker FJ, Jaffe R, Demmler G, Kearney D, et al. Acute myocarditis. Rapid diagnosis by PCR in children. Circulation. 1994;90(1):330–9.

    Article  CAS  PubMed  Google Scholar 

  127. Wojnicz R, Nowalany-Kozielska E, Wojciechowska C, Glanowska G, Wilczewski P, Niklewski T, et al. Randomized, placebo-controlled study for immunosuppressive treatment of inflammatory dilated cardiomyopathy: two-year follow-up results. Circulation. 2001;104(1):39–45.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute for Genetics of Heart Diseases (IfGH), Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany

    Stefan Peischard, Huyen Tran Ho & Guiscard Seebohm

Authors
  1. Stefan Peischard
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Huyen Tran Ho
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Guiscard Seebohm
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Guiscard Seebohm .

Editor information

Editors and Affiliations

  1. Cardiac Electrophysiology Division, Ion Channel Study Center, Life Science Academy, Lucknow, India

    Onkar N. Tripathi

  2. Department of Physiology and Biophysics, Dalhousie University, Halifax, Canada

    T. Alexander Quinn

  3. Institute for Experimental Cardiovascular Medicine, University Heart Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany

    Ursula Ravens

Rights and permissions

Reprints and permissions

Copyright information

© 2023 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Peischard, S., Ho, H.T., Seebohm, G. (2023). Viral Myocarditis. In: Tripathi, O.N., Quinn, T.A., Ravens, U. (eds) Heart Rate and Rhythm. Springer, Cham. https://doi.org/10.1007/978-3-031-33588-4_24

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-33588-4_24

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-33587-7

  • Online ISBN: 978-3-031-33588-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation