Chapter 5 : Antigenic Mimicry between Self and Coxsackievirus Proteins Leads to Both Humoral and Cellular Autoimmunity to Heart Proteins

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Antigenic Mimicry between Self and Coxsackievirus Proteins Leads to Both Humoral and Cellular Autoimmunity to Heart Proteins, Page 1 of 2

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Enteroviruses have evolved mechanisms for terminal shutoff of host protein synthesis. These mechanisms involve viral protease 2A degradation of the cellular p220 protein cap-dependent binding complex or degradation of poly(A)-binding protein. These mechanisms are not operative in all infected cells that replicate these viruses to the usual titers of 100 to 2,500 virions per cell. Indeed, many types of cells, including cardiac fibroblasts, that are permissive for replication of coxsackievirus group B (CVB) strains exhibit little to no viral cytopathic effects during production of virus for days to weeks. Three major mechanisms probably cause cardiac dysfunction in patients with viral myocarditis and dilated cardiomyopathy (DCM). These include: injury directly due to virus infection and replication in the heart, damage mediated by specific and nonspecific host defense responses to the infection, and autoimmunity to cardiac antigens triggered by virus infection. A conundrum exists between poor cardiac function in patients with severe chronic myocarditis or DCM and the often minimal pathologic alterations found in their heart tissues upon autopsy. Antigenic mimicry at the T-cell level has been demonstrated between heart antigens and various pathogens, including group A streptococci, , chlamydia, cytomegalovirus, and CVB. Adoptive transfer of lymphocytes from ANT-reactive patients also transferred myocarditis into severe combined immunodeficient mice. Finally, murine T cells from CVB3-infected mice respond to adenine nucleotide translocator (ANT), again indicating not only that different pathogens may share the same epitope but also that a single pathogen is likely to have multiple distinct mimicking epitopes with diverse heart proteins.

Citation: Huber S, Gauntt C. 2000. Antigenic Mimicry between Self and Coxsackievirus Proteins Leads to Both Humoral and Cellular Autoimmunity to Heart Proteins, p 57-68. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch5
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1. Abel, L.,, J. Kalil,, J. Cunha,, and E. Neto. 1997. Molecular mimicry between cardiac myosin and Trypanosoma cruzi antigen B13: identification of a B13-driven human T cell clone that recognizes cardiac myosin. Braz. J. Med. Biol. Res. 30: 1305 1308.
2. Anderson, J.,, E. Hammond,, and R. Menlove,. 1987. Determining humoral and cellular-immune components in myocarditis: complementary diagnostic role of immunofluorescence microscopy in the evaluation of endomyocardial biopsy specimens, p. 233 244. In C. Kawai, and W. Abelmann (ed.), Pathogenesis of Myocarditis and Cardiomyopathy Update I. University of Tokyo Press; Tokyo, Japan.
3. Aretz, H. 1987. Myocarditis: the Dallas criteria. Hum. Pathol. 18: 619 624.
4. Bachmaier, K.,, N. Neu,, L. de la Maza,, S. Pal,, A. Hessel,, and J. Penninger. 1999. Chlamydia infections and heart disease linked through antigenic mimicry. Science 283: 1335 1339.
5. Badorff, C.,, G. Lee,, B. Lamphear,, M. Martone,, K. Campbell,, R. Rhoads,, and K. Knowlton. 1999. Enteroviral protease 2A cleaves dystrophin: evidence of cytoskeletal disruption in an acquired cardiomyopathy. Nat. Med. 5: 320 326.
6. Bick, R.,, J. Liao,, T. King,, A. LeMaistre,, J. McMillan,, and L. Buja. 1997. Temporal effects of cytokines on neonatal cardiac myocyte Ca 2+ transient and adenylate cyclase activity. Am. J. Physiol. 272: H1937 H1944.
7. Bolte, H.-D.,, and P. Schultheiss. 1978. Immunologic results in myocardial diseases. Postgrad. Med. J. 54: 500 503.
8. Bowles, N.,, P. Richardson,, E. Olsen,, and L. Archard. 1986. Detection of coxsackie B virus-specific RNA sequences in myocardial biopsy samples from patients with myocarditis and dilated cardiomyopathy. Lancet i: 1120 1122.
9. Caforio, A.,, E. Bonifacio,, and J. Stewart 1990. Novel organ-specific circulating cardiac autoantibodies in dilated cardiomyopathy. J. Am. Coll. Cardiol. 15: 1527 1534.
10. Caforio, A.,, J. Goldman,, A. Haven,, K. Baig,, and W. McKenna. 1996. Evidence for autoimmunity to myosin and other heart-specific autoantigens in patients with cardiomyopathy and their relatives. Int. J. Cardiol. 54: 157 163.
11. Caforio, A.,, P. Keeling,, and E. Zachara. 1994. Evidence from family studies for autoimmunity in dilated cardiomyopathy. Lancet 344: 773 777.
12. Chen, J.,, R. Lorenz,, J. Goldberg,, and P. Allen. 1991. Identification and characterization of a T cell-inducing epitope of bovine ribonuclease that can be restricted by multiple class II molecules. J. Immunol. 147: 3672 3678.
13. Cook, D.,, M. Beck,, T. Cofman,, S. Kirby,, J. Sheridan,, I. Pragnell,, and O. Smithies. 1995. Requirement of MlP-la for an inflammatory response to viral infection. Science 269: 1583 1585.
14. Cunningham, M.,, S. Antone,, J. Gulizia,, M. McManus,, V. Fishchetti,, and C. Gauntt. 1992. Cytotoxic and viral neutralizing antibodies cross react with streptococcal M protein, enteroviruses, and human cardiac myosin. Proc. Natl. Acad. Sci. USA 89: 1320.
15. Donermeyer, D.,, K. Bersel,, P. Allen,, and S. Smith. 1995. Myocarditis-inducing epitope of myosin binds constitutively and stably to I-Ak on antigen-presenting cells in the heart. J. Exp. Med. 182: 1291 1299.
16. Fairweather, D.,, C. Lawson,, A. Chapman,, C. Brown,, T. Booth,, J. Papadimitriou,, and G. Shellam. 1998. Wild isolates of murine cytomegalovirus induce myocarditis and antibodies that cross-react with virus and cardiac myosin. Immunology 94: 263 270.
17. Felix, J.,, B. von Kreuter,, and C. Santos-Bush. 1993. Mimicry of heart cell surface epitopes in primary anti- Trypanosoma cruzi Lyt 2+ T lymphocytes. Clin. Immunol. Immunopathol. 68: 141 146.
18. Freeman, G.,, J. Colston,, M. Zabalgoitia,, and B. Chandrasekar. 1998. Contractile depression and expression of proinflammatory cytokines and iNOS in viral myocarditis. Am. J. Physiol. 274( 1 part 2): H249 H258.
19. Gauntt, C., 1988. The possible role of viral variants in pathogenesis, p. 159 179. In H. Friedman, and M. Bendinelli (ed.), Coxsackievirus—a General Update, vol. 1. Plenum Publishing Co., New York, N.Y.
20. Gauntt, C. 1997. Roles of the humoral response in coxsackievirus B-induced disease. Curr. Top. Microbiol. Immunol. 223: 259 282.
21. Gauntt, C.,, H. Arizpe,, A. Higdon,, H. Wood,, D. Bowers,, M. Rozeck,, and R. Crawley. 1995. Molecular mimicry: anti-coxsackievirus B3 neutralizing antibodies and myocarditis. J. Immunol. 154: 2983 2995.
22. Gauntt, C.,, A. Higdon,, H. Arizpe,, M. Tamayo,, R. Crawley,, R. Henkel,, M. Pereira,, S. Tracy,, and M. Cunningham. 1993. Epitopes shared between coxsackievirus B3 (CVB3) and normal heart tissue contribute to CVB3-induced murine myocarditis. Clin. Immunol. Immunopathol. 68: 129 134.
23. Gauntt, C.,, A. Higdon,, D. Bowers,, E. Maull,, J. Wood,, and R. Crawley. 1993. What lessons can be learned from animal model studies in viral heart disease? Scand. J. Infect. Dis. 88( Suppl.): 49 65.
24. Gauntt, C.,, P. Sakkinen,, N. Rose,, and S. Huber,. 2000. Picornaviruses: immunopathology and autoimmunity, p. 313 329. In M. Cunningham, and R. Fujinami (ed.), Effects of Microbes on the Immune System. Lippincott-Raven Publishers, Philadelphia, Pa.
25. Gauntt, C.,, C. Winfey,, H. Wood,, A. Karaganis,, C. Lee,, and M. Cunningham. 1996. Anti-coxsackievirus group B antibodies and inflammatory heart disease, p. 257-270. In G. Pandalai (ed.), Recent Research Developments in Antimicrobial Agents and Chemotherapy. Research Signpost, Trivandrum, India.
26. Grist, N.,, and E. Bell. 1973. A six year study of coxsackievirus B infection in heart disease. J. Hyg. (London) 73: 165 172.
27. Guilherme, L.,, E. Cunha-Neto,, V. Coelho,, R. Snitcowsky,, P. Pomerantzeff,, R. Assis,, F. Pedra,, J. Neumann,, A. Goldberg,, M. Patarroyo,, F. Pileggi,, and J. Kalil. 1995. Human heart-infiltrating T-cell clones from rheumatic heart disease patients recognize both streptococcal and cardiac proteins. Circulation 92: 415 420.
28. Herzum, M.,, V. Rupert,, B. Kuytz,, H. Jomau,, I. Nakamura,, and B. Maisch. 1994. Coxsackievirus B3 infection leads to cell death of cardiac myoctytes. J. Mol. Cell. Cardiol. 26: 907 913.
29. Huber, S. 1997. Animal models of human disease—autoimmunity in myocarditis: relevance of animal models. Clin. Immunol. Immunopathol. 83: 93 102.
30. Huber, S. 1997. Coxsackievirus-induced myocarditis is dependent on distinct immunopathogenic responses in different strains of mice. Lab. Investig. 76: 691 701.
31. Huber, S.,, and M. Cunningham. 1996. Streptococcal M protein peptide with similarity to myosin induces CD4 + T cell dependent myocarditis in MRL/++ mice and induces partial tolerance against coxsackieviral myocarditis. J. Immunol. 156: 3528 3534.
32. Huber, S.,, and P. Lodge. 1986. Coxsackievirus B3 myocarditis: identification of different mechanisms in DBA/2 and Balb/c mice. Am. J. Pathol. 122: 284.
33. Huber, S.,, A. Moraska,, and M. Cunningham. 1994. Alterations in major histocompatibility complex association of myocarditis induced by coxsackievirus B3 (CVB3) mutants selected with monoclonal antibodies to group A streptococci. Proc. Natl. Acad. Sci. USA 91: 5543 5547.
34. Huber, S.,, J. Polgar,, P. Schultheiss,, and P. Schwimmbeck. 1994. Augmentation of pathogenesis of coxsackievirus B3 infections in mice by exogenous administration of interleukin-1 and interleukin-2. J. Virol. 68: 195 206.
35. Huber, S. A.,, C. J. Gauntt,, and P. Sakkinen. 1998. Enteroviruses and myocarditis: viral pathogenesis through replication, cytokine induction and immunopathogenicity. Adv. Virus Res. 51: 35 80.
36. Kerekatte, V.,, B. Keiper,, C. Badorff,, A. Cai,, K. Knowlton,, and R. Rhoads. 1999. Cleavage of poly(A)-binding protein by coxsackievirus 2A protease in vitro and in vivo: another mechanism for host protein synthesis shutoff? J. Virol. 73: 709 711.
37. Khaw, B.,, J. Narula,, A. Sharaf,, P. Nicol,, J. Southern,, and M. Carles. 1995. SR-Ca 2+ ATPase as an autoimmunogen in experimental myocarditis. Eur. Heart J. 16( Suppl. O): 92 96.
38. Klingel, K.,, C. Hohenadl,, A. Canu,, M. Albrecht,, M. Seemann,, G. Mall,, and R. Kandolf. 1992. Ongoing enterovirus-induced myocarditis is associated with persistent heart muscle infection: quantitative analysis of virus replication, tissue damage and inflammation. Proc. Natl. Acad. Sci. USA 89: 314 318.
39. Klingel, K.,, and R. Kandolf. 1993. The role of enterovirus replication in the development of acute and chronic heart muscle disease in different immunocompetent mouse strains. Scand. J. Infect. Dis. 88( Suppl.): 79 85.
40. Klingel, K.,, S. Stephans,, M. Sauter,, R. Zell,, B. McManus,, B. Bultmann,, and R. Kandolf. 1996. Pathogenesis of murine enterovirus myocarditis: virus dissemination and immune cell targets. J. Virol. 70: 8888 8895.
41. Koontz, C.,, and C. Ray. 1971. The role of coxsackie group B virus infections in sporadic myopericarditis. Am. Heart J. 82: 750 758.
42. Kuan, A.,, W. Chamberlain,, S. Malkiel,, H. Lieu,, S. Factor,, B. Diamond,, and B. L. Kotzin. 1999. Genetic control of autoimmune myocarditis mediated by myosin-specific antibodies. Immunogen 49: 79 85.
43. Kubota, T.,, C. McTiernan,, C. Frye,, S. Slawson,, B. Lemster,, A. Koretsky,, A. Demetris,, and A. Feldman. 1997. Dilated cardiomyopathy in transgenic mice with cardiac-specific overexpression of tumor necrosis factor-alpha. Circ. Res. 81: 627 635.
44. Lane, J.,, D. Neumann,, A. Lafond-Walker,, A. Herkowitz,, and N. Rose. 1992. Interleukin 1 or tumor necrosis factor can promote coxsackie B3-induced myocarditis in resistant B10.A mice. J. Exp. Med. 175: 1123 1129.
45. Lane, J.,, D. Neumann,, A. Lanfond-Walker,, A. Herskowitz,, and N. Rose. 1993. Role of IL-1 and tumor necrosis factor in coxsackievirus-induced autoimmune myocarditis. J. Immunol. 151: 1682 1690.
46. Leslie, K.,, R. Blay,, C. Haisch, R Lodge, A. Weller, and S. Huber. 1989. Clinical and experimental aspects of viral myocarditis. Clin. Microbiol. Rev. 2: 191 203.
47. Liao, L.,, J. Sindhwani,, L. Leinwand,, B. Diamond,, and S. Factor. 1993. Cardiac a-myosin heavy chains differ in their induction of myocarditis: identification of pathogenic epitopes. J. Clin. Investig. 92: 2877 2882.
48. Liao, L.,, R. Sindhwani,, M. Rojkind,, S. Factor,, L. Leinwand,, and B. Diamond. 1995. Antibody-mediated autoimmune myocarditis depends on genetically determined target organ sensitivity. J. Exp. Med. 187: 1123 1131.
49. Limas, C. 1996. Autoimmunity in dilated cardiomyopathy and the major histocompatibility complex. Int. J. Cardiol. 54: 113 116.
50. Limas, C.,, and C. Limas. 1993. Immune-mediated modulation of B-adrenoreceptor function in human dilated cardiomyopathy. Clin. Immunol. Immunopathol. 68: 204 207.
51. Lodge, R.,, M. Herzum,, J. Olszewski,, and S. Huber. 1987. Coxsackievirus B3-myocarditis: acute and chronic forms of the disease caused by different immunopathogenic mechanisms. Am. J. Pathol. 128: 455 463.
52. Loudon, R.,, A. Moraska,, S. Huber,, P. Schwimmbeck,, and H.-P. Schultheiss. 1991. An attenuated variant of coxsackievirus B3 preferentially induces immunoregulatory T cells in vivo. J. Virol. 65: 5813 5819.
53.Lutton, C, and C. Gauntt. 1986. Coxsackievirus B3 infection alters plasma membrane of neonatal kin fibroblasts. J. Virol. 60: 294296.
54. Maisch, B. 1989. Autoreactivity to the cardiac myocyte, connective tissue and the extracellular matrix in heart disease and postcardiac injury. Springer Semin. Immunopathol. 11: 369 396.
55. Maisch, B., 1984. Diagnostic relevance of humoral and cell mediated immune reactions in patients with acute myocarditis and congestive cardiomyopathy, p. 1327 1338. In E. Chazov,, V. Smirnov,, and R. Oganov (ed.), Cardiology. Plenum Publishing Co., New York, N.Y.
56. Maisch, B.,, E. Bauer,, M. Cirsi,, and K. Kocksiek. 1993. Cytolytic cross-reactive antibodies directed against the cardiac membrane and viral proteins in coxsackievirus B3 and B4 myocarditis. Circulation 87( Suppl. IV): 49 65.
57. Maisch, B.,, M. Herzum,, G. Hufuagel,, C. Bethge,, and U. Schonian. 1995. Immunosuppressive treatment for myocarditis and dilated cardiomyopathy. Eur. Heart J. 16( Suppl. O): 153 161.
58. Maisch, B.,, R. Trostel-Soder,, E. Stechmesser,, P. Berg,, and K. Kochsiek. 1982. Diagnostic relevance of humoral and cell-mediated immune reactions in patients with acute viral myocarditis. Clin. Exp. Immunol. 48: 533 545.
59. McManus, B.,, C. Gauntt,, and R. Cassling. 1987. Immunopathologic basis of myocardial injury. Cardiovasc. Clin. 18: 163 184.
60. Muckelbauer, J.,, and M. Rossman. 1997. The structure of coxsackievirus B3. Curr. Top. Microbiol. Immunol. 223: 191 208.
61. Neu, N.,, K. Beisel,, M. Traystman,, N. Rose,, and S. Craig. 1987. Autoantibodies specific for the cardiac myosin isoform are found in mice susceptible to coxsackievirus B3-induced myocarditis. J. Immunol. 138: 2488 2492.
62. Neu, N.,, N. Rose,, K. Beisel,, A. Herskowitz,, G. Gurri-Glass,, and S. Craig. 1987. Cardiac myosin induces myocarditis in genetically predisposed mice. J. Immunol. 139: 3630 3636.
63. Neumann, D.,, G. Allen,, C. Narins,, N. Rose,, and A. Herskowitz,. 1993. Heart autoantibodies in human myocarditis and cardiomyopathy: virus and skeletal muscle cross-reactivity, p. 325 334. In H. Figulla,, R. Kandolf,, and B. McManus (ed.), Idiopathic Dilated Cardiomyopathy. Springer-Verlag, Berlin, Germany.
64. Neumann, D.,, C. Burek,, K. Baughman,, N. Rose,, and A. Herskowitz. 1990. Circulating heart-reactive autoantibodies in patients with myocarditis or dilated cardiomyopathy. J. Am. Coll. Cardiol. 16: 839 846.
65. Neumann, D.,, J. Lane,, S. Wulff,, G. Allen,, A. Lafond-Walker,, A. Herskowitz,, and N. Rose. 1992. In vivo deposition of myosin-specific autoantibodies in the hearts of mice with experimental autoimmune myocarditis. J. Immunol. 148: 3806 3811.
66. Neumann, D.,, N. Rose,, A. Ansari,, and A. Herkowitz. 1994. Induction of multiple heart autoantibodies in mice with coxsackievirus B3- and cardiac myosin-induced autoimmune myocarditis. J. Immunol. 152: 343 350.
67. Pallansch, M. 1988. Epidemiology of Group B Coxsackieviruses. Plenum Publishing Corp., New York, N.Y.
68. Quarantino, S.,, C. Thorpe,, P. Travers,, and M. Londei. 1995. Similar antigenic surfaces, rather than sequence homology, dictate T-cell epitope molecular mimicry. Proc. Nad. Acad. Sci. USA 92: 10398 10402.
69. Rose, N.,, A. Herskowitz,, D. Newumann, andN. Neu. 1988. Autoimmune myocarditis: a paradigm of postinfection autoimmune disease. Immunol. Today 9: 117 118.
70. Rose, N.,, N. Neu,, D. Neumann,, and A. Herskowitz,. 1988. Myocarditis: a postinfectious autoimmune disease, p. 139 147. In H.-P. Schultheiss (ed.), New Concepts in Viral Heart Disease. Springer-Verlag, Berlin, Germany.
71. Rose, N.,, D. Neumann,, and A. Herskowitz. 1992. Coxsackievirus myocarditis. Adv. Intern. Med. 37: 411 429.
72. Rueckert, R. 1996. Picornaviruses, 3rd ed. Lippincott-Raven, Philadelphia, Pa.
73. Saegusa, J.,, B. Prabhakar,, K. Essani,, P. McClintock,, Y. Fukuda,, V. Ferrna,, and A. Notkins. 1986. Monoclonal antibody to coxsackievirus B4 reacts with myocardium. J. Infect. Dis. 153: 372 373.
74. Sato, S.,, R. Tsutsumi,, A. Burke,, G. Carson,, V. Porro,, Y. Seko,, K. Okumura,, R. Kawana,, and S. Virmani. 1994. Persistence of replicating coxsackievirus B3 in the athymic murine heart is associated with development of myocarditic lesions. J. Gen. Virol. 75: 2911 2924.
75. Schmidt, N.,, R. Magoffin,, and E. Lennette. 1973. Association of group B coxsackie viruses with cases of pericarditis, myocarditis, or pleurodynia by demonstration of immunoglobulin M antibody. Infect. Immun. 8: 341 348.
76. Schultheiss, H. 1989. The significance of autoantibodies against the ACP/ATP carrier for the pathogenesis of myocarditis and dilated cardiomyopathy—clinical and experimental data. Springer Semin. Immunopathol. 11: 15 30.
77. Schwimmbeck, P.,, C. Badorff,, H. Schultheiss,, and B. Strauer. 1994. Transfer of human myocarditis into severe combined immunodeficient mice. Circ. Res. 75: 156 164.
78. Schwimmbeck, P.,, C. Badorff,, K. Schulze,, and H.-P. Schultheiss,. 1997. The significance of T cell responses in human myocarditis, p. 65 76. In H.-P. Schultheiss, and P. Schwimmbeck (ed.), The Role of Immune Mechanisms in Cardiovascular Disease. Springer-Verlag, Berlin, Germany.
79. Schwimmbeck, P.,, H.-P. Schultheiss,, and B. Strauer. 1989. Identification of a main auto-immunogenic epitope of the adenine nucleotide translocator which cross reacts with coxsackievirus B3: use in the diagnosis of myocarditis and dilated cardiomyopathy. Circulation 80( Suppl. II): 665 669.
80. Schwimmbeck, P.,, N. Schwimmbeck,, H. Schultheis,, and B. Strauer. 1993. Mapping of antigenic determinants of the adenine-nucleotide translocator and coxsackie B3 virus with synthetic peptides: use for the diagnosis of viral-heart disease. Clin. Immunol. Immunopathol. 68: 135 140.
81. Seko, Y.,, H. Matsuda,, K. Kato,, Y. Hashimoto,, H. Yagita,, K. Okumura,, and Y. Yazaki. 1993. Expression of intercellular adhesion molecule-1 in murine hearts with acute myocarditis caused by coxsackievirus B3. J. Clin. Invest. 91: 1327 1336.
82. Shikman, A.,, and M. Cunningham. 1994. Immunological mimicry between N-acetyl-β-D-glucosamine and cytokeratin peptides: evidence for a microbially driven antikeratin antibody response. J. Immunol. 152: 4375 4387.
83. Shikman, A.,, N. Greenspan,, and M. Cunningham. 1993. A subset of mouse monoclonal antibodies cross-react with cytoskeletal proteins and group A streptococcal M proteins recognizes N-acetyl-β-D-glucosamine. J. Immunol. 151: 3902 3913.
84. Smith, S.,, and P. Allen. 1991. Myosin-induced acute myocarditis is a T cell-mediated disease. J. Immunol. 147: 2141 2147.
85. Smith, W. 1970. Coxsackie B myopericarditis in adults. Am. Heart J. 80: 34 46.
86. Theofilopoulos, A. 1995. The basis for autoimmunity. Part I. Mechanisms of aberrant self-recognition. Immunol. Today 16: 90 98.
87. Theofilopoulos, A. 1995. The basis for autoimmunity. Part II. Genetic predisposition. Immunol. Today 16: 150 159.
88. Thcofilopoulos, A. 1997. Mechanisms and Genetics of Autoimmunity. Springer-Verlag, Berlin, Germany.
89. Tracy, S.,, V. Wiegand,, B. McManus,, C. Gauntt,, M. PaUansch,, M. Beck,, and N. Chapman. 1990. Molecular approaches to enteroviral diagnosis in idiopathic cardiomyopathy and myocarditis. J. Am. Coll. Cardiol. 15: 1688 1694.
90. Traystman, D.,, and K. Beisel. 1991. Genetic control of coxsackievirus B3-induced heart-specific autoantibodies associated with chronic myocarditis. Clin. Exp. Immunopathol. 86: 291 298.
91. Traystman, M.,, L. Chow,, B. M. McManus,, A. Herskowitz,, M. Nesbitt,, and K. Beisel. 1991. Susceptibility to coxsackievirus B3-induced chronic myocarditis maps near the murine Tcr and Myhc alpha loci on chromosome 14. Am. J. Pathol. 138: 721 732.
92. Ulrich, G.,, U. Kuhl,, B. Melzner,, I. Janda,, B. Schafer,, and H.-P. Schultheiss,. 1988. Antibodies against the adenosine di/triphosphate carrier cross-react with the Ca ++ channel-functional and biochemical data, p. 226 235. In H.-P. Schultheiss (ed.), New Concepts in Viral Heart Disease. Springer-Verlag, Berlin, Germany.
93. Van Houten, N.,, P. Bouchard,, A. Moraska,, and S. Huber. 1991. Selection of an attenuated coxsackievirus B3 variant using a monoclonal antibody reactive to myocyte antigen. J. Virol. 65: 1286 1290.
94. Wallukat, G.,, A. Kayser,, and A. Wollenberger. 1995. The beta 1-adrenoceptor as antigen: functional aspects. Eur. Heart J. 16( Suppl. O): 85 88.
95. Weller, A.,, K. Simpson,, M. Herzum,, N. Van Houten,, and S. Huber. 1989. Coxsackievirus B3 induced myocarditis: virus receptor antibodies modulate myocarditis. J. Immunol. 143: 1843 1850.
96. Wessely, R.,, K. Klingel,, L. Santana,, N. Dalton,, M. Hongo,, W. Jonathan Lederer,, R. Kandolf,, and K. Knowlton. 1998. Transgenic expression of replication-restricted enteroviral genomes in heart muscle induces defective excitation-contraction coupling and dilated cardiomyopathy. J. Clin. Investig. 102: 1444 1453.
97. Why, H.,, T. Meany,, P. Richardson,, E. Olsen,, N. Bowles,, L. Cunningham,, C. Freeke,, and L. Archard. 1994. Clinical and prognostic significance of detection of enteroviral RNA in the myocardium of patients with myocarditis or dilated cardiomyopathy. Circulation 89: 2582 2589.
98. Wolff, P.,, U. Kuhl,, and H. Schultheiss. 1989. Laminin distribution and autoantibodies to laminin in dilated cardiomyopathy and myocarditis. Am. Heart J. 117: 1303 1309.
99. Woodruff, J. 1980. Viral myocarditis. Am. J. Pathol. 101: 425 483.
100. Woodruff, J.,, and J. Woodruff. 1974. Involvement of T lymphocytes in the pathogenesis of coxsackievirus B3 heart disease. J. Immunol. 113: 1726 1734.
101. Wucherpfennig, K.,, and J. Strominger. 1995. Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell 80: 695 705.

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