Chapter 31 : Immunology of the Coxsackieviruses

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The coxsackieviruses are the best-studied group of nonpolio enteroviruses. Unlike that of the polioviruses, the immune reactions of the human or murine (in models of human disease) hosts of infections by the coxsackieviruses are an important component of the diseases generally induced by these viruses. The first T-cell epitope of the coxsackieviruses to be recognized is located in the 2C protein and is held in common with other human enteroviruses; the predominant lymphocyte population proliferating in response to the 2C epitope was CD4 T cells. In a study using the CVB4-induced murine pancreatitis model, CVB4-inoculated nude and severe combined immunodeficient SCID mice had increased viral replication in the pancreas and increased mortality at early stages of disease, but CD4 knockout mice were protected. This work suggests that CD4 T-cell responses in the pancreas (a tissue which, in intraperitoneally inoculated mice, achieves coxsackievirus titers as high or higher and more rapidly than serum titers observed in viremia) may be essential for survival during early virus-induced disease, but at later times these cells participate in increased inflammatory disease. In conclusion, immune responses against coxsackieviruses have been explored through the use of murine models of virus-induced heart and pancreatic diseases. The diversity of inbred mouse lines and viral strains leaves the significance of studies to be resolved by comparison with human disease or by a methodical dissection of the immune response to coxsackieviruses generated in the various murine strains.

Citation: Chapman N, Tracy S, Gauntt C. 2002. Immunology of the Coxsackieviruses, p 391-403. In Semler B, Wimmer E (ed), Molecular Biology of Picornavirus. ASM Press, Washington, DC. doi: 10.1128/9781555817916.ch31
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Image of FIGURE 1a

Conservation of amino acid sequence of coxsackieviruses (B group) at sites containing Τ epitopes, antibody-binding sites, and neutralizing antibody sites. Surface residues are indicated ( ). Genbank Accession numbers: CVB1, M16560; CVB2, AF085363; CVB3-1, -2, M88483; CVB3-3, U57056; CVB4, D00149; CVB5, AF105342; CVB6, AF105342. — indicates identical to residue indicated above; indicates a deletion relative to the peptide sequence; a indicates antibody-binding site; b indicates neutralizing antibody-binding site; с indicates Τ epitope. 1, reference ; 2, reference ; 3, reference ; 4, reference ; 5, reference ; 6, reference ; 7, reference .

Citation: Chapman N, Tracy S, Gauntt C. 2002. Immunology of the Coxsackieviruses, p 391-403. In Semler B, Wimmer E (ed), Molecular Biology of Picornavirus. ASM Press, Washington, DC. doi: 10.1128/9781555817916.ch31
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Image of FIGURE 1b

Conservation of amino acid sequence of coxsackieviruses (B group) at sites containing Τ epitopes, antibody-binding sites, and neutralizing antibody sites. Surface residues are indicated ( ). Genbank Accession numbers: CVB1, M16560; CVB2, AF085363; CVB3-1, -2, M88483; CVB3-3, U57056; CVB4, D00149; CVB5, AF105342; CVB6, AF105342. — indicates identical to residue indicated above; indicates a deletion relative to the peptide sequence; a indicates antibody-binding site; b indicates neutralizing antibody-binding site; с indicates Τ epitope. 1, reference ; 2, reference ; 3, reference ; 4, reference ; 5, reference ; 6, reference ; 7, reference .

Citation: Chapman N, Tracy S, Gauntt C. 2002. Immunology of the Coxsackieviruses, p 391-403. In Semler B, Wimmer E (ed), Molecular Biology of Picornavirus. ASM Press, Washington, DC. doi: 10.1128/9781555817916.ch31
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1. Anderson, D. R.,, C. M. Carthy,, J. E. Wilson,, D. Yang,, D. V. Devine,, and B. M. McManus. 1997. Complement component 3 interactions with coxsackievirus B3 capsid proteins: innate immunity and the rapid formation of splenic antiviral germinal centers. J. Virol. 71: 8841 8845.
2. Anderson, D. R.,, J. E. Wilson,, C. M. Carthy,, D. Yang,, R. Kandolf,, and B. M. McManus. 1996. Direct interactions of coxsackievirus B3 with immune cells in the splenic compartment of mice susceptible or resistant to myocarditis. J. Virol. 70: 4632 4645.
3. Auvinen, P.,, M. J. Makela,, M. Roivainen,, M. Kallajoki,, R. Vainionpaa,, and T. Hyypia. 1993 Mapping of antigenic sites of coxsackievirus B3 by synthetic peptides. APMIS 101: 517 528.
4. Baboonian, C.,, M. J. Davies,, J. C. Booth,, and W. J. McKenna. 1997. Coxsackie B viruses and human heart disease. Curr. Top. Microbiol. Immunol. 223: 31 52.
5. Bachmann, M. R.,, and R. M. Zinkernagel. 1996. Virus structure, antibody response and virus serotypes. Immunol. Today 17: 553 558.
6. Baixeras, E.,, G. Kroemer,, E. Cuende,, C. Marquez,, L. Bosca,, J. E. Ales Martinez,, and C. Martinez. 1993. Signal transduction pathways involved in B-cell induction. Immunol. Rev. 132: 5 47.
7. Beatrice, S. T.,, M. G. Katze,, B. A. Zajac,, and R. L. Crowell. 1980. Induction of neutralizing antibodies by the coxsackievirus B3 virion polypeptide, VP2. Virology 104: 426 438.
8. Beck, M. A.,, and S. M. Tracy. 1989. Murine cell-mediated immune response recognizes an enterovirus group-specific antigen(s). J. Virol. 63: 4148 4156.
9. Beck, M. A.,, and S. M. Tracy. 1990. Evidence for a group-specific enteroviral antigen(s) recognized by human T cells. J. Clin. Microbiol. 28: 1822 1827.
10. Beck, M. A.,, S. Tracy,, B. A. Coller,, N. M. Chapman,, G. Hufnagel,, J. E. Johnson,, and G. Lomonossoff. 1992. Comoviruses and enteroviruses share a T cell epitope. Virology 186: 238 246.
11. Beisel, K. W.,, J. Srinivasappa,, and B. S. Prabhakar. 1991. Identification of a putative shared epitope between coxsackie virus B4 and alpha cardiac myosin heavy chain. Clin. Exp. Immunol. 86: 49 55.
12. Blay, R.,, K. Simpson,, K. Leslie,, and S. Huber. 1989. Coxsackievirus-induced disease. CD4+ cells initiate both myocarditis and pancreatitis in DBA/2 mice. Am. J. Pathol. 135: 899 907.
13. Born, W.,, C. Cady,, J. Jones-Carson,, A. Mukasa,, M. Lahn,, and R. O’Brien. 1999. Immunoregulatory functions of gamma delta T cells. Adv. Immunol. 71: 77 144.
14. Carroll, M. C. 1998. The role of complement and complement receptors in induction and regulation of immunity. Annu. Rev. Immunol. 16: 545 568.
15. Cello, J.,, A. Samuelson,, P. Stalhandske,, B. Svennerholm,, S. Jeansson,, and M. Forsgren. 1993. Identification of group-common linear epitopes in structural and nonstructural proteins of enteroviruses by using synthetic peptides. J. Clin. Microbiol. 31: 911 916.
16. Cello, J.,, O. Strannegard,, and B. Svennerholm. 1996. A study of the cellular immune response to enteroviruses in humans: identification of cross-reactive T cell epitopes on the structural proteins of enteroviruses. J. Gen. Virol. 77: 2097 2108.
17. Chang, K. H.,, P. Auvinen,, T. Hyypia,, and G. Stanway. 1989. The nucleotide sequence of coxsackievirus A9; implications for receptor binding and enterovirus classification. J. Gen. Virol. 70: 3269 3280.
18. Chang, K. H.,, C. Day,, J. Walker,, T. Hyypia,, and G. Stanway. 1992. The nucleotide sequences of wild-type coxsackievirus A9 strains imply that an RGD motif in VP1 is functionally significant. J. Gen. Virol. 73: 621 626.
19. Chapman, N.,, C. Gauntt,, and S. Tracy. 1999. Enteroviruses. In The Encychpedia of Life Sciences. Macmillian Reference Limited, London, United Kingdom.
20. Chapman, N. M.,, A. Ragland,, J. S. Leser,, K. Hofling,, S. Willian,, B. L. Semler,, and S. Tracy. 2000. A group B coxsackievirus/poliovirus 5' nontranslated region chimera can act as an attenuated vaccine strain in mice. J. Virol. 74: 4047 4056.
21. Chapman, N. M.,, A. Ramsingh,, and S. Tracy. 1997. Genetics of coxsackievirus virulence. Curr. Top. Microbiol. Immunol. 223: 227 258.
22. Cho, C. T.,, K. K. Feng,, V. P. McCarthy,, and M. F. Lenahan. 1982. Role of antiviral antibodies in resistance against coxsackievirus B3 infection: interaction between preexisting antibodies and an interferon inducer. Infect. Immun. 37: 720 727.
23. Chow, L. H.,, K. W. Beisel,, and B. M. McManus. 1992. Enteroviral infection of mice with severe combined immunodeficiency. Evidence for direct viral pathogenesis of myocardial injury. Lab. Invest. 66: 24 31.
24. Cunningham, M. W.,, S. M. Antone,, J. M. Gulizia,, B. M. McManus,, V. A. Fischetti,, and C. J. Gauntt. 1992. Cytotoxic and viral neutralizing antibodies crossreact with streptococcal M protein, enteroviruses, and human cardiac myosin. Proc. Natl. Acad. Sci. USA 89: 1320 1324.
25. Eggers, H. J.,, and T. Mertens. 1986. Persistence of coxsackie B virus-specific IgM. Lancet 2: 284
26. Estrin, M.,, and S. A. Huber. 1987. Coxsackievirus B3-induced myocarditis. Autoimmunity is L3T4 + T helper cell and IL-2 independent in BALB/c mice. Am. J. Pathol. 127: 335 341.
27. Fohlman, J.,, N. G. Ilback,, G. Friman,, and B. Morein. 1990. Vaccination of Balb/c mice against enteroviral mediated myocarditis. Vaccine 8: 381 384
28. Fohlman, J.,, K. Pauksen,, B. Morein,, U. Bjare,, N. G. Ilback,, and G. Friman. 1993. High yield production of an inactivated coxsackie B3 adjuvant vaccine with protective effect against experimental myocarditis. Scand. J. Infect. Dis. Suppl. 88: 103 108.
29. Frisk, G.,, and H. Diderholm. 1997. Antibody responses to different strains of coxsackie B4 virus in patients with newly diagnosed type I diabetes mellitus or aseptic meningitis. J. Infect. 34: 205 210.
30. Frisk, G.,, G. Friman,, T. Tuvemo,, J. Fohlman,, and H. Diderholm. 1992. Coxsackie B virus IgM in children at onset of type 1 (insulin-dependent) diabetes mellitus: evidence for IgM induction by a recent or current infection. Diabetologia 35: 249 253.
31. Gauntt, C. J. 1997. Roles of the humoral response in coxsackievirus B-induced disease. Curr. Top. Microbiol. Immunol. 223: 259 282.
32. Gauntt, C. J.,, H. M. Arizpe,, A. L. Higdon,, M. M. Rozek,, R. Crawley,, and M. W. Cunningham. 1991. Anti-coxsackievirus B3 neutralizing antibodies with pathological potential. Eur. Heart J. 12( Suppl. D): 124 129.
33. Gauntt, C. J.,, E. K. Godeny,, C. W. Lutton,, H. M. Arizpe,, N. M. Chapman,, S. M. Tracy,, G. E. Revtyak,, A. J. Valente,, and M. M. Rozek,. 1989. Mechanism(s) of coxsackievirus-induced acute myocarditis in the mouse, p. 161 182. In L. M. de la Maza, and E. M. Peterson (ed.), Medical Virology 8. Plenum, New York, N.Y.
34. Gauntt, C. J.,, A. L. Higdon,, H. M. Arizpe,, M. R. Tamayo,, R. Crawley,, R. D. Henkel,, M. E. Pereira,, S. M. Tracy,, and M. W. Cunningham. 1993. Epitopes shared between coxsackievirus B3 (CVB3) and normal heart tissue contribute to CVB3-induced murine myocarditis. Clin. Immunol. Immunopathol. 68: 129 134.
35. Gauntt, C. J.,, R. E. Paque,, M. D. Trousdale,, R. J. Gudvangen,, D. T. Barr,, G. J. Lipotich,, T. J. Nealon,, and P. S. Duffey. 1983. Temperature-sensitive mutant of coxsackievirus B3 establishes resistance in neonatal mice that protects them during adolescence against coxsackievirus B3-induced myocarditis. Infect. Immun. 39: 851 864.
36. Gauntt, C. J.,, P. Sakkinen,, N. R. Rose,, and S. A. Huber,. 1998. Picomaviruses: immunopathology and autoimmunity, In M. W. Cunningham, and R. S. Fujinami (ed.), Effects of Microbes on the Immune System. Lippincott-Raven Publishers, Philadelphia, Pa.
37. Gauntt, C. J.,, S. M. Tracy,, N. Chapman,, H. J. Wood,, P. C. Kolbeck,, A. G. Karaganis,, C. L. Winfrey,, and M. W. Cunningham. 1995. Coxsackievirus-induced chronic myocarditis in murine models. Eur. Heart J. 16( Suppl. O): 56 58.
38. Gebhard, J. R.,, C. M. Perry,, S. Harkins,, T. Lane,, I. Mena,, V. C. Asensio,, and I. L. Campbell. 1998. Coxsackievirus B3-induced myocarditis: perforin exacerbates disease, but plays no detectable role in virus clearance. Am. J. Pathol. 153: 417 428.
39. Godeny, E. K.,, H. M. Arizpe,, and C. J. Gauntt. 1988. Characterization of the antibody response in vaccinated mice protected against coxsackievirus B3-induced myocarditis. Viral Immunol. 1: 305 313.
40. Godeny, E. K.,, and C. J. Gauntt. 1986. Involvement of natural killer cells in coxsackievirus B3-induced murine myocarditis. J. Immunol. 137: 1695 1702.
41. Godeny, E. K.,, and C. J. Gauntt. 1987. Murine natural killer cells limit coxsackievirus B3 replication. J. Immunol. 139: 913 918.
42. Godeny, E. K.,, and C. J. Gauntt. 1987. In situ immune autoradiographic identification of cells in heart tissues of mice with coxsackievirus B3-induced myocarditis. Am. J. Pathol. 129: 267 276.
43. Gomez, R.,, E. Lascano,, and M. Berria. 1991. Murine acinar pancreatitis preceding necrotizing myocarditis after coxsackievirus B3 inoculation. J. Med. Virol. 35: 71 75.
44. Graham, S.,, E. C. Wang,, O. Jenkins,, and L. K. Borysiewicz. 1993. Analysis of the human T-cell response to picomaviruses: identification of T-cell epitopes close to B-cell epitopes in poliovirus. J. Virol. 67: 1627 1637.
45. Graves, P. M.,, J. M. Norris,, M. A. Pallansch,, I. C. Gerling,, and M. Rewers. 1997. The role of enteroviral infections in the development of IDDM: limitations of current approaches. Diabetes 46: 161 168.
46. Guthrie, M.,, P. A. Lodge,, and S. A. Huber. 1984. Cardiac injury in myocarditis induced by coxsackievirus group B, type 3 in Balb/c mice is mediated by Lyt 2 + cytolytic lymphocytes. Cell. Immunol. 88: 558 567.
47. Haarmann, C. M.,, P. L. Schwimmbeck,, T. Mertens,, H. P. Schultheiss,, and B. E. Strauer. 1994. Identification of serotype-specific and nonserotype-specific B-cell epitopes of coxsackie B virus using synthetic peptides. Virology 200: 318 389.
48. Hahn, S.,, R. Gehri,, and P. Erb. 1995. Mechanism and biological significance of CD4-mediated cytotoxicity. Immunol. Rev. 146: 57 79.
49. Halim, S.,, and A. I. Ramsingh. 2000. A point mutation in VP1 of coxsackievirus B4 alters antigenicity. Virology 269: 86 94.
50. Harkonen, T.,, T. Hovi,, and M. Roivainen. 1997. Expression of coxsackievirus B4 proteins VP0 and 2C in Escherichia coli and generation of virus protein recognizing antisera. J. Virol. Methods 69: 147 158.
51. Hashimoto, I.,, and T. Komatsu. 1978. Myocardial changes after infection with Coxsackie virus B3 in nude mice. Br. J. Exp. Pathol. 59: 13 20.
52. Hathaway, L. j.,, and J. P. Kraehenbuhl. 2000. The role of M cells in mucosal immunity. Cell Mol. Life Sci. 57: 323 332.
53. Heim, A.,, I. Grumbach,, S. Hake,, G. Muller,, P. Pring-Akerblom,, G. Mall,, and H. R. Figulla. 1997. Enterovirus heart disease of adults: a persistent, limited organ infection in the presence of neutralizing antibodies. J. Med. Virol. 53: 196 204.
54. 54 Heim, A.,, S. Zeuke,, S. Weiss,, W. Ruschewski,, and I. M. Grumbach. 2000. Transient induction of cytokine production in human myocardial fibroblasts by coxsackievirus B3. Circ. Res. 86: 753 759.
55. Heinz, B. A.,, and D. O. Cliver. 1988. Coxsackievirus-cell interactions that initiate infection in porcine ileal explants. Arch. Virol. 101: 35 47.
56. Heinz, B. A.,, D. O. Cliver,, and B. Donohoe. 1987. Enterovirus replication in porcine ileal expiants. J. Gen. Virol. 68: 2495 2499.
57. Henke, A.,, S. Huber,, A. Stelzner,, and J. L. Whitton. 1995. The role of CD8 + T lymphocytes in coxsackievirus B3-induced myocarditis. J. Virol. 69: 6720 6728.
58. Hewat, E. A.,, T. C. Marlovits,, and D. Blaas. 1998. Structure of a neutralizing antibody bound monovalently to human rhinovirus 2. J. Virol. 72: 4396 4402.
59. Hillerdal, G.,, G. Frisk,, O. Nettelbladt,, and H. Diderholm. 1992. High frequency of IgM antibodies to coxsackie B virus in sarcoidosis patients and patients with asbestos-related lesions. Sarcoidosis 9: 39 42.
60. Hogle, J. M.,, and D. J. Filman. 1989. The antigenic structure of poliovirus. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 323: 467 478.
61. Hou, J.,, C. Said,, D. Franchi,, P. Dockstader,, and N. K. Chatterjee. 1994. Antibodies to glutamic acid decarboxylase and P2-C peptides in sera from coxsackie virus B4-infected mice and IDDM patients. Diabetes 43: 1260 1266.
62. Hovi, T.,, and M. Roivainen. 1993. Peptide antisera targeted to a conserved sequence in poliovirus capsid VP1 cross-react widely with members of the genus Enterovirus. J. Clin. Microbiol. 31: 1083 1087.
63. Huber, S. A. 1997. Coxsackievirus-induced myocarditis is dependent on distinct immunopathogenic responses in different strains of mice. Lab. Invest. 76: 691 701.
64. Huber, S.A.,, R. C. Budd,, K. Rossner,, and M. K. Newell. 1999. Apoptosis in coxsackievirus B3-induced myocarditis and dilated cardiomyopathy. Ann. N. Y. Acad. Sci. 887: 181 190.
65. Huber, S. A.,, and M. W. 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.
66. 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.
67. Huber, S. A.,, N. Heintz,, and R. Tracy. 1988. Coxsackievirus B-3-induced myocarditis. Virus and actinomycin D treatment of myocytes induces novel antigens recognized by cytolytic T lymphocytes. J. Immunol. 141: 3214 3219.
68. Huber, S. A.,, L. P. Job,, K. R. Auld,, and J. F. Woodruff. 1981. Sex-related differences in the rapid production of cytotoxic spleen cells active against uninfected myofibers during coxsackievirus B-3 infection. J. Immunol. 126: 1336 1340.
69. Huber, S. A.,, L. P. Job,, and J. F. Woodruff. 1980. Lysis of infected myofibers by coxsackievirus B-3-immune T lymphocytes. Am. J. Pathol. 98: 681 694.
70. Huber, S. A.,, and P. A. Lodge. 1984. Coxsackievirus B-3 myocarditis in Balb/c mice. Evidence for autoimmunity to myocyte antigens. Am. J. Pathol. 116: 21 29.
71. Huber, S. A.,, A. Moraska,, and M. Cunningham. 1994. Alterations in major histocompatibility complex association of myocarditis induced by coxsackievirus B3 mutants selected with monoclonal antibodies to group A streptococci. Proc. Natl. Acad. Sci. USA 91: 5543 5547.
72. Huber, S. A.,, A. Mortensen,, and G. Moulton. 1996. Modulation of cytokine expression by CD4+ T cells during coxsackievirus B3 infections of BALB/c mice initiated by cells expressing the gamma delta + T-cell receptor. J. Virol. 70: 3039 3044.
73. Huber, S. A.,, and B. Pfaeffle. 1994. Differential Thl and Th2 cell responses in male and female BALB/c mice infected with coxsackievirus group B type 3. J. Virol. 68: 5126 5132.
74. Huber, S.,, J. Polgar,, A. Moraska,, M. Cunningham,, P. Schwimmbeck,, and P. Schultheiss. 1993. T lymphocyte responses in CVB3-induced murine myocarditis. Scand. J. Infect. Dis. Suppl. 88: 67 78.
75. Huber, S. A.,, 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.
76. Hufnagel, G.,, N. Chapman,, and S. Tracy. 1995. A non-cardiovirulent strain of coxsackievirus B3 causes myocarditis in mice with severe combined immunodeficiency syndrome. Eur. Heart. J. 16( Suppl. O): 18 19.
77. Kang, Y.,, N. K. Chatterjee,, M. J. Nodwell,, and J. W. Yoon. 1994. Complete nucleotide sequence of a strain of coxsackie B4 virus of human origin that induces diabetes in mice and its comparison with nondiabetogenic coxsackie B4 JBV strain. J. Med. Virol. 44: 353 361.
78. Karlsson, M. G.,, and J. Ludvigsson. 1998. Peptide from glutamic acid decarboxylase similar to coxsackie B virus stimulates IFN-gamma mRNA expression in Th1-like lymphocytes from children with recent-onset insulin-dependent diabetes mellitus. Acta Diabetol. 35: 137 144.
79. Katze, M. G.,, and R. L. Crowell. 1980. Immunological studies of the group B coxsackieviruses by the sandwich enzyme-linked immunosorbent assay (ELISA) and immunoprecipitation. J. Gen. Virol. 50: 357 367.
80. Kaufman, D. L.,, M. G. Lander,, M. Clare-Salzler,, M. A. Atkinson,, N. K. Maclaren,, and A. J. Tobin. 1992. Autoimmunity to two forms of glutamate decarboxylase in insulin-dependent diabetes mellitus. J. Clin. Invest. 89: 283 292.
81. Kishimoto, C.,, Y. Kuroki,, Y. Hiraoka,, H. Ochiai,, M. Kurokawa,, and S. Sasayama. 1994. Cytokine and murine coxsackievirus B3 myocarditis. Interleukin-2 suppressed myocarditis in the acute stage but enhanced the condition in the subsequent stage. Circulation 89: 2836 2842.
82. Knowlton, K. U.,, and C. Badorff. 1999. The immune system in viral myocarditis: maintaining the balance. Circ. Res. 85: 559 561.
83. Kutubuddin, M.,, J. Simons,, and M. Chow. 1992. Identification of T-helper epitopes in the VP1 capsid protein of poliovirus. J. Virol. 66: 3042 3047.
84. Lane, J. R.,, D. A. Neumann,, A. Lafond-Walker,, A. Herskowitz,, and N. R. Rose. 1991. LPS promotes CB3-induced myocarditis in resistant B10.A mice. Cell. Immunol. 136: 219 233.
85. Lane, J. R.,, D. A. Neumann,, A. Lafond-Walker,, A. Herskowitz,, and N. R. 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.
86. Lanier, L. L. 1998. NK cell receptors. Annu. Rev. Immunol. 16: 359 393.
87. Leclerc, C.,, E. Deriaud,, V. Mimic,, and S. van der Werf. 1991. Identification of a T-cell epitope adjacent to neutralization antigenic site 1 of poliovirus type 1. J. Virol. 65: 711 718.
88. Leipner, C.,, M. Borchers,, I. Merkle,, and A. Stelzner. 1999. Coxsackievirus B3-induced myocarditis in MHC class II-deficient mice. J. Hum. Virol. 2: 102 114.
89. Leslie, K.,, R. Blay,, C. Haisch,, A. Lodge,, A. Weller,, and S. Huber. 1989. Clinical and experimental aspects of viral myocarditis. Clin. Microbiol. Rev. 2: 191 203.
90. Liu, P.,, J. Penninger,, K. Aitken,, M. Sole,, and T. Mak. 1995. The role of transgenic knockout models in defining the pathogenesis of viral heart disease. Eur. Heart J. 16( Suppl. O): 25 27.
91. Lonnrot, M.,, H. Hyoty,, M. Knip,, M. Roivainen,, P. Kulmala,, P. Leinikki,, H. K. Akerblom, and Childhood Diabetes in Finland Study Group. 1996. Antibody cross-reactivity induced by the homologous regions in glutamic acid decarboxylase (GAD65) and 2C protein of coxsackievirus B4. Clin. Exp. Immunol. 104: 398 405.
92. Luppi, P.,, W. A. Rudert,, M. M. Zanone,, G. Stassi,, G. Trueco,, D. Finegold,, G. J. Boyle,, P. Del Nido,, F. X. McGowan, Jr.,, and M. Trueco. 1998. Idiopathic dilated cardiomyopathy: a superantigen-driven autoimmune disease. Circulation 98: 777 785.
93. Magnius, L. O.,, L. H. Saleh,, T. Vikerfors,, and H. Norder. 1988. A solid-phase reverse immunosorbent test for the detection of enterovirus IgM. J. Virol. Methods 20: 73 82.
94. Mahon, B. P.,, K. Katrak,, and K. H. Mills. 1992. Antigenic sequences of poliovirus recognized by T cells: serotype-specific epitopes on VP1 and VP3 and cross-reactive epitopes on VP4 defined by using CD4+ T-cell clones. J. Virol. 66: 7012 7020.
95. Maisch, B.,, E. Bauer,, M. Cirsi,, and K. Kochsiek. 1993. Cytolytic cross-reactive antibodies directed against the cardiac membrane and viral proteins in coxsackievirus B3 and B4 myocarditis. Characterization and pathogenetic relevance. Circulation 87( Suppl. 5): 49 65.
96. Mandelboim, O.,, S. B. Wilson,, M. Vales-Gomez,, H. T. Reyburn,, and J. L. Strominger. 1997. Loading of MHC I with peptides with P8 K prevents binding of inhibitory receptor. Proc. Natl. Acad. Sci. USA 94: 4604 4609.
97. Martino, T. A.,, P. Liu,, M. Petric,, and M. J. Sole,. 1995. Enteroviral myocarditis and dilated cardiomyopathy: a review of clinical and experimental studies, p. 291 351. In H. Rotbart (ed.), Human Enterovirus Injections. ASM Press, Washington, D.C.
98. Mateu, M. G. 1995. Antibody recognition of picomaviruses and escape from neutralization: a structural view. Virus Res. 38: 1 24.
99. Matteucci, D.,, M. Paglianti,, A. M. Giangregorio,, M. R. Capobianchi,, F. Dianzani,, and M. Bendinelli. 1985. Group B coxsackieviruses readily establish persistent infections in human lymphoid cell lines. J. Virol. 56: 651 654.
100. McPhee, F.,, R. Zell,, B. Y. Reimann,, P. H. Hofschneider,, and R. Kandolf. 1994. Characterization of the N-terminal part of the neutralizing antigenic site I of coxsackievirus B4 by mutation analysis of antigen chimeras. Virus Res. 34: 139 151.
101. Mertens, T.,, U. Pika,, and H. J. Eggers. 1983. Cross antigenicity among enteroviruses as revealed by immunoblot technique. Virology 129: 431 442.
102. Minor, P. D.,, M. Ferguson,, D. M. Evans,, J. W. Almond,, and J. P. Icenogle. 1986. Antigenic structure of polioviruses of serotypes 1, 2 and 3. J. Gen. Virol. 67: 1283 1291.
103. Misbah, S. A.,, G. P. Spickett,, P. C. Ryba,, J. M. Hockaday,, J. S. Kroll,, C. Sherwood,, J. B. Kurtz,, E. R. Moxon,, and H. M. Chapel. 1992. Chronic enteroviral meningoencephalitis in agammaglobulinemia: case report and literature review. J. Clin. Immunol. 12: 266 270.
104. Mondino, A.,, A. Khoruts,, and M. K. Jenkins. 1996. The anatomy of T-cell activation and tolerance. Proc. Natl. Acad. Sci. USA 93: 2245 2252.
105. Muckelbauer, J. K.,, M. Kremer,, I. Minor,, G. Diana,, F. J. Dutko,, J. Groarke,, D. C. Pevear,, and M. G. Rossmann. 1995. The structure of coxsackievirus B3 at 3.5 A resolution. Structure 3: 653 667.
106. Muckelbauer, J. K.,, and M. G. Rossmann. 1997. The structure of coxsackievirus B3. Curr. Top Microbiol. Immunol. 223: 191 208.
107. Muir, P.,, F. Nicholson,, A. J. Tilzey,, M. Signy,, T. A. English,, and J. E. Banatvala. 1989. Chronic relapsing pericarditis and dilated cardiomyopathy: serological evidence of persistent enterovirus infection. Lancet 1: 804 807.
108. Muir, P.,, F. Nicholson,, S. J. Illavia,, T. S. McNeil,, J. F. Ajetunmobi,, H. Dunn,, W. G. Starkey,, K. N. Reetoo,, N. R. Cary,, J. Parameshwar,, and J. E. Banatvala. 1996. Serological and molecular evidence of enterovirus infection in patients with end-stage dilated cardiomyopathy. Heart 76: 243 249.
109. Neu, N.,, R. Klieber,, M. Fruhwirth,, and P. Berger. 1991. Cardiac myosin-induced myocarditis as a model of postinfectious autoimmunity. Eur. Heart J. 12 (Suppl. O): 117 120.
110. Neu, N.,, B. Ploier,, and C. Ofner. 1990. Cardiac myosin-induced myocarditis. Heart autoantibodies are not involved in the induction of the disease. J. Immunol. 145: 4094 4100.
111. Neumann, D. A.,, J. R. Lane,, G. S. Allen,, A. Herskowitz,, and N. R. Rose. 1993. Viral myocarditis leading to cardiomyopathy: do cytokines contribute to pathogenesis? Clin. Immunol. Immunopathol. 68: 181 190.
112. Neutra, M. R.,, A. Frey,, and J. P. Kraehenbuhl. 1996. Epithelial M cells: gateways for mucosal infection and immunization. Cell 86: 345 348.
113. Opavsky, M. A.,, J. Penninger,, K. Aitken,, W. H. Wen,, F. Dawood,, T. Mak,, and P. Liu. 1999. Susceptibility to myocarditis is dependent on the response of alphabeta T lymphocytes to coxsackieviral infection. Circ. Res. 85: 551 558.
114. Page, G. S.,, A. G. Mosser,, J. M. Hogle,, D. J. Filman,, R. R. Rueckert,, and M. Chow. 1988. Three-dimensional structure of poliovirus serotype 1 neutralizing determinants. J. Virol. 62: 1781 1794.
115. Parker, D. C. 1993. T cell-dependent B cell activation. Annu. Rev. Immunol. 11: 331 360.
116. Pozzetto, B.,, O. G. Gaudin,, F. R. Lucht,, J. Hand,, and A. Ros. 1990. Detection of immunoglobulin G, M, and A antibodies to enterovirus structural proteins by immunoblot technique in echovirus type 4-infected patients. J. Virol. Methods 29: 143 155.
117. Pulli, T.,, M. Roivainen,, T. Hovi,, and T. Hyypia. 1998. Induction of neutralizing antibodies by synthetic peptides representing the C terminus of coxsackievirus A9 capsid protein VP1. J. Gen. Virol. 79: 2249 2253.
118. Ramsingh, A.,, N. Chapman,, and S. Tracy. 1997. Coxsackieviruses and diabetes. Bioessays 19: 793 800.
119. Ramsingh, A. L.,, W. T. Lee,, D. N. Collins,, and L. E. Armstrong. 1999. T cells contribute to disease severity during coxsackievirus B4 infection. J. Virol. 73: 3080 3086.
120. Ramsingh, A.,, J. Slack,, J. Silkworth,, and A. Hixson. 1989. Severity of disease induced by a pancreatropic coxsackie B4 virus correlates with the H-2Kq locus of the major histocompatibility complex. Virus Res. 14: 347 358.
121. Reigel, F.,, F. Burkhardt,, and U. Schilt. 1985. Cross-reactions of immunoglobulin M and G antibodies with enterovirus-specific viral structural proteins. J. Hyg. (London) 95: 469 481.
122. Reimann, B. Y.,, R. Zell,, and R. Kandolf. 1991. Mapping of a neutralizing antigenic site of coxsackievirus B4 by construction of an antigen chimera. J. Virol. 65: 3475 3480.
123. Robinson, J. A.,, J. B. O’Connell,, L. M. Roeges,, E. O. Major,, and R. M. Gunnar. 1981. Coxsackie B3 myocarditis in athymic mice. Proc. Soc. Exp. Biol. Med. 166: 80 91.
124. Roivainen, M.,, T. Hyypia,, L. Piirainen,, N. Kalkkinen,, G. Stanway,, and T. Hovi. 1991. RGD-dependent entry of coxsackievirus A9 into host cells and its bypass after cleavage of VP1 protein by intestinal proteases. J. Virol. 65: 4735 4740.
125. Romagnani, S. 1996. Thl and Th2 in human diseases. Clin. Immunol. Immunopathol. 80: 225 235.
126. Romero, J. R.,, C. Price,, and J. J. Dunn. 1997. Genetic divergence among the group B coxsackieviruses. Curr. Top. Microbiol. Immunol. 223: 97 152.
127. Rose, N. R.,, and S. L. Hill. 1996. The pathogenesis of postinfectious myocarditis. Clin. Immunol. Immunopathol. 80: S92 S99.
128. Rose, N. R.,, and S. L. Hill. 1996. Autoimmune myocarditis. Int. J. Cardiol. 54: 171 175.
129. Rossmann, M. G.,, E. Arnold,, J. W. Erickson,, E. A. Frankenberger,, J. P. Griffith,, H. J. Hecht,, J. E. Johnson,, G. Kamer,, M. Luo,, A. G. Mosser,, R. R. Rueckert,, B. Sherry,, and G. Vriend. 1985. Structure of a human common cold virus and functional relationship to other picomaviruses. Nature 317: 145 153.
130. Samuelson, A.,, M. Forsgren,, B. Johansson,, B. Wahren,, and M. Sallberg. 1994. Molecular basis for serological cross-reactivity between enteroviruses. Diagn. Lab Immunol. 1: 336 341.
131. Sato, S.,, R. Tsutsumi,, A. Burke,, G. Carlson,, V. Porro,, Y. Seko,, K. Okumura,, R. Kawana,, and R. 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.
132. Satoh, M.,, G. Tamura,, I. Segawa,, A. Tashiro,, K. Hiramori,, and R. Satodate. 1996. Expression of cytokine genes and presence of enteroviral genomic RNA in endomyocardial biopsy tissues of myocarditis and dilated cardiomyopathy. Virch. Arch. 427: 503 509.
133. Schloot, N. C.,, B. O. Roep,, D. R. Wegmann,, L. Yu,, T. B. Wang,, and G. S. Eisenbarth. 1997. T-cell reactivity to GAD65 peptide sequences shared with coxsackie virus protein in recent-onset IDDM, post-onset IDDM patients and control subjects. Diabetologia 40: 332 338.
134. Schmidt, N. J.,, R. L. Magoffin,, and E. H. 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.
135. Schnurr, D. P.,, Y. Cao,, and N. J. Schmidt. 1984. Coxsackievirus B3 persistence and myocatditis in N:NIH(S) II nu/nu and +/nu mice. J. Gen. Virol. 65: 1197 1201.
136. Schultheiss, H. P.,, and H. D. Bolte. 1985. Immunological analysis of auto-antibodies against the adenine nucleotide translocator in dilated cardiomyopathy. J. Mol. Cell. Cardiol. 17: 603 617.
137. Schwimmbeck, P. L.,, C. Badorff,, G. Rohn,, K. Schulze,, and H. P. Schultheiss. 1996. The role of sensitized T-cells in myocarditis and dilated cardiomyopathy. Int. J. Cardiol. 54: 117 125.
138. Schwimmbeck, P. L.,, S. A. Huber,, and H. P. Schultheiss. 1997. Roles of T cells in coxsackievirus B-induced disease. Curr. Top. Microbiol. Immunol. 223: 283 303.
139. See, D. M.,, and J. G. Tilles. 1997. Occurrence of coxsackievirus hepatitis in baby rabbits and protection by a formalin-inactivated polyvalent vaccine. Proc. Soc. Exp. Biol. Med. 216: 52 56.
140. Seko, Y.,, S. Ishiyama,, T. Nishikawa,, T. Kasajima,, M. Hiroe,, N. Kagawa,, K. Osada,, S. Suzuki,, H. Yagita,, K. Okumura,, and Y. Yazaki. 1995. Restricted usage of T cell receptor V alpha-V beta genes in infiltrating cells in the hearts of patients with acute myocarditis and dilated cardiomyopathy. J. Clin. Invest. 96: 1035 1041.
141. Seko, Y.,, N. Takahashi,, M. Azuma,, H. Yagita,, K. Okumura,, and Y. Yazaki. 1998. Effects of in vivo administration of anti-B7-l/B7-2 monoclonal antibodies on murine acute myocarditis caused by coxsackievirus B3. Circ. Res. 82: 613 618.
142. Seko, Y.,, N. Takahashi,, M. Azuma,, H. Yagita,, K. Okumura,, and Y. Yazaki. 1998. Expression of costimulatory molecule CD40 in murine heart with acute myocarditis and reduction of inflammation by treatment with anti-CD40L/B7-1 monoclonal antibodies. Circ. Res. 83: 463 469.
143. Seko, Y.,, N. Takahashi,, H. Yagita,, K. Okumura,, and Y. Yazaki. 1997. Expression of cytokine mRNAs in murine hearts with acute myocarditis caused by coxsackievirus B3. J. Pathol. 183: 105 108.
144. Seko, Y.,, H. Tsuchimochi,, T. Nakamura,, K. Okumura,, S. Naito,, K. Imataka,, J. Fujii, R Takaku, and Y. Yazaki. 1990. Expression of major histocompatibility complex class I antigen in murine ventricular myocytes infected with coxsackievirus B3. Circ. Res. 67: 360 367.
145. Seko, Y.,, H. Yagita,, K. Okumura,, and Y. Yazaki. 1994. T-cell receptor V beta gene expression in infiltrating cells in murine hearts with acute myocarditis caused by coxsackievirus B3. Circulation 89: 2170 2175.
146. Seko, Y.,, E. Yoshifumi,, H. Yagita,, K. Okumura,, and Y. Yazaki. 1996. Restricted usage of T-cell receptor V alpha genes in infiltrating cells in murine hearts with acute myocarditis caused by coxsackievirus B3. J. Pathol. 178: 330 334.
147. Sherry, B.,, A. G. Mosser,, R. J. Colonno,, and R. R. Rueckert. 1986. Use of monoclonal antibodies to identify four neutralization immunogens on a common cold picornavirus, human rhinovirus 14. J. Virol. 57: 246 257.
148. Shikhman, A. R.,, N. S. Greenspan,, and M. W. Cunningham. 1993. A subset of mouse monoclonal antibodies cross-reactive with cytoskeletal proteins and group A streptococcal M proteins recognizes N-acetyl-beta-D-glu-cosamine. J. Immunol. 151: 3902 3913.
149. Sicinski, P.,, J. Rowinski,, J. B. Warchol,, Z. Jarzabek,, W. Gut,, B. Szczygiel,, K. Bielecki,, and G. Koch. 1990. Poliovirus type 1 enters the human host through intestinal M cells. Gastroenterology 98: 56 58.
150. Skyllouriotis, P.,, M. Skyllouriotis-Lazarou,, S. Natter,, R. Steiner,, S. Spitzauer,, S. Kapiotis,, P. Valent,, A. M. Hirschl,, S. E. Guber,, G. Laufer,, G. Wollenek,, E. Wolner,, M. Wimmer,, and R. Valenta. 1999. IgG subclass reactivity to human cardiac myosin in cardiomyopathy patients is indicative of a Th1-like autoimmune disease. Clin. Exp. Immunol. 115: 236 247.
151. Smith, S. C.,, and P. M. Men. 1991. Myosin-induced acute myocarditis is a T cell-mediated disease. J. Immunol. 147: 2141 2147.
152. Takada, H.,, C. Kishimoto,, Y. Hiraoka,, and A. Rager-Zisman. 1995. Therapy with immunoglobulin suppresses myocarditis in a murine coxsackievirus B3 model. Antiviral and anti-inflammatory effects. Circulation 92: 1604 1611.
153. Tilzey, A. J.,, M. Signy,, and J. E. Banatvala. 1986. Persistent coxsackie B virus specific IgM response in patients with recurrent pericarditis. Lancet 1: 1491 1492.
154. Toniolo, A.,, T. Onodera,, G. Jordan,, J. W. Yoon,, and A. L. Notkins. 1982. Virus-induced diabetes mellitus. Glucose abnormalities produced in mice by the six members of the coxsackie B virus group. Diabetes 31: 496 499.
155. Torfason, E. G.,, M. Pallansch,, C. B. Reimer,, C. Wickliffe,, and H. L. Keyserling. 1992. Immunoglobulin class and subclass-specific monoclonal antibody sandwich ELISA for the detection of antibodies against coxsackieviruses B, types 1-5. J. Virol. Methods 37: 289 303.
156. Tracy, S.,, N. M. Chapman,, R. Rubocki,, and M. Beck,. 1995. The host immune response to enterovirus infections, p. 175 191. In H. Rotbart (ed.), Human Enterovirus Infections. ASM Press, Washington, D.C.
157. Tracy, S.,, K. Hofling,, S. Pirruccello,, P. H. Lane,, S. M. Reyna,, and C. J. Gauntt. 2001. Group B coxsackievirus myocarditis and pancreatitis: connection between viral virulence phenotypes in mice. J. Med. Virol. 62: 70 81.
158. Tu, Z.,, N. M. Chapman,, G. Hufnagel,, S. Tracy,, J. R. Romero,, W. H. Barry,, L. Zhao,, K. Currey,, and B. Shapiro. 1995. The cardiovirulent phenotype of coxsackievirus B3 is determined at a single site in the genomic 5’ nontranslated region. J. Virol. 69: 4607 4618.
159. Vella, C.,, and H. Festenstein. 1992. Coxsackievirus B4 infection of the mouse pancreas: the role of natural killer cells in the control of virus replication and resistance to infection. J. Gen. Virol. 73: 1379 1386.
160. Vreugdenhil, G. R.,, A. Geluk,, T. H. Ottenhoff,, W. J. Melchers,, B. O. Roep,, and J. M. Galama. 1998. Molecular mimicry in diabetes mellitus: the homologous domain in coxsackie B virus protein 2C and islet autoan-tigen GAD65 is highly conserved in the coxsackie B-like enteroviruses and binds to the diabetes associated HLA-DR3 molecule. Diabetologia 41: 40 46.
161. Vuorinen, T.,, R. Vainionpaa,, H. Kettinen,, and T. Hyypia. 1994. Coxsackievirus B3 infection in human leukocytes and lymphoid cell lines. Blood 84: 823 829.
162. Vuorinen, T.,, R. Vainionpaa,, R. Vanharanta,, and T. Hyypia. 1996. Susceptibility of human bone marrow cells and hematopoietic cell lines to coxsackievirus B3 infection. J. Virol. 70: 9018 9023.
163. Vuorinen, T.,, R. Vainionpaa,, J. Heino,, and T. Hyypia. 1999. Enterovirus receptors and virus replication in human leukocytes. J. Gen. Virol. 80: 921 927.
164. Weller, A. H.,, M. Hall,, and S. A. Huber. 1992. Polyclonal immunoglobulin therapy protects against cardiac damage in experimental coxsackievirus-induced myocarditis. Eur. Heart J. 13: 115 119.
165. Wolfram, L. J.,, K. W. Beisel,, A. Herskowitz,, and N. R. Rose. 1986. Variations in the susceptibility to coxsackievirus B3-induced myocarditis among different strains of mice. J. Immunol. 136: 1846 1852.
166. Woodruff, J.F. 1980. Viral myocarditis. A review. Am. J. Pathol. 101: 425 484.
167. Yoon, J. W.,, M. Austin,, T. Onodera,, and A. L. Notkins. 1979. Isolation of a virus from the pancreas of a child with diabetic ketoacidosis. N. Engl. J. Med. 300: 1173 1179.
168. Yousef, G. E.,, E. J. Bell,, G. F. Mann,, V. Murugesan,, D. G. Smith,, R. A. McCartney,, and J. F. Mowbray. 1988. Chronic enterovirus infection in patients with postviral fatigue syndrome. Lancet 1: 146 150.
169. Ytterberg, S. R.,, M. L. Mahowald,, and R. P. Messner. 1987. Coxsackievirus B 1-induced polymyositis. Lack of disease expression in nu/nu mice. J. Clin. Invest. 80: 499 506.
170. Zamorano, P.,, A. Wigdorovitz,, M. Perez-Filgueira,, C. Carrillo,, J. M. Escribano,, A. M. Sadir,, and M. V. Borca. 1995. A 10-amino-acid linear sequence of VP1 of foot and mouth disease virus containing B- and T-cell epitopes induces protection in mice. Virology 212: 614 621.
171. Zaragoza, C.,, C. Ocampo,, M. Saura,, M. Leppo,, X. Q. Wei,, R. Quick,, S. Moneada,, F. Y. Liew,, and C. J. Lowenstein. 1998. The role of inducible nitric oxide synthase in the host response to coxsackievirus myocarditis. Proc. Natl. Acad. Sci. USA 95: 2469 2474.
172. Zhang, H.,, P. Morgan-Capner,, N. Latif,, Y. A. Pandolfino,, W. Fan,, M. J. Dunn,, and L. C. Archard. 1997. Coxsackievirus B3-induced myocarditis. Characterization of stable attenuated variants that protect against infection with the cardiovirulent wild-type strain. Am. J. Pathol. 150: 2197 2207.
173. Zinkernagel, R. M., 1997. Virus-induced immunopathology, p. 163 180. In N. Nathanson (ed.), Viral Pathogenesis. Lippincott-Raven, Philadelphia, Pa.

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