Chapter 31 : Immunology of the Coxsackieviruses

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in

Immunology of the Coxsackieviruses, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555817916/9781555812102_Chap31-1.gif /docserver/preview/fulltext/10.1128/9781555817916/9781555812102_Chap31-2.gif


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

Key Concept Ranking

Complement System
Immune Systems
Amino Acids
Humoral Immune Response
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


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
Permissions and Reprints Request Permissions
Download as Powerpoint
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
Permissions and Reprints Request Permissions
Download as Powerpoint


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. 71:88418845.
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. 70:46324645.
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 101:517528.
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. 223:3152.
5. Bachmann, M. R.,, and R. M. Zinkernagel. 1996. Virus structure, antibody response and virus serotypes. Immunol. Today 17:553558.
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. 132:547.
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 104:426438.
8. Beck, M. A.,, and S. M. Tracy. 1989. Murine cell-mediated immune response recognizes an enterovirus group-specific antigen(s). J. Virol. 63:41484156.
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. 28:18221827.
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 186:238246.
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. 86:4955.
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. 135:899907.
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. 71:77144.
14. Carroll, M. C. 1998. The role of complement and complement receptors in induction and regulation of immunity. Annu. Rev. Immunol. 16:545568.
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. 31:911916.
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: 20972108.
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. 70:32693280.
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. 73:621626.
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. 74:40474056.
21. Chapman, N. M.,, A. Ramsingh,, and S. Tracy. 1997. Genetics of coxsackievirus virulence. Curr. Top. Microbiol. Immunol. 223:227258.
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. 37:720727.
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. 66:2431.
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 89:13201324.
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. 127:335341.
27. Fohlman, J.,, N. G. Ilback,, G. Friman,, and B. Morein. 1990. Vaccination of Balb/c mice against enteroviral mediated myocarditis. Vaccine 8:381384
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. 88:103108.
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. 34:205210.
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 35:249253.
31. Gauntt, C. J. 1997. Roles of the humoral response in coxsackievirus B-induced disease. Curr. Top. Microbiol. Immunol. 223:259282.
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):124129.
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. 161182. 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. 68:129134.
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. 39:851864.
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):5658.
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. 153:417428.
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. 1:305313.
40. Godeny, E. K.,, and C. J. Gauntt. 1986. Involvement of natural killer cells in coxsackievirus B3-induced murine myocarditis. J. Immunol. 137:16951702.
41. Godeny, E. K.,, and C. J. Gauntt. 1987. Murine natural killer cells limit coxsackievirus B3 replication. J. Immunol. 139:913918.
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. 129:267276.
43. Gomez, R.,, E. Lascano,, and M. Berria. 1991. Murine acinar pancreatitis preceding necrotizing myocarditis after coxsackievirus B3 inoculation. J. Med. Virol. 35:7175.
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. 67:16271637.
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 46:161168.
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. 88:558567.
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 200:318389.
48. Hahn, S.,, R. Gehri,, and P. Erb. 1995. Mechanism and biological significance of CD4-mediated cytotoxicity. Immunol. Rev. 146:5779.
49. Halim, S.,, and A. I. Ramsingh. 2000. A point mutation in VP1 of coxsackievirus B4 alters antigenicity. Virology 269:8694.
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 69:147158.
51. Hashimoto, I.,, and T. Komatsu. 1978. Myocardial changes after infection with Coxsackie virus B3 in nude mice. Br. J. Exp. Pathol. 59:1320.
52. Hathaway, L. j.,, and J. P. Kraehenbuhl. 2000. The role of M cells in mucosal immunity. Cell Mol. Life Sci. 57: 323332.
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. 53:196204.
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. 86:753759.
55. Heinz, B. A.,, and D. O. Cliver. 1988. Coxsackievirus-cell interactions that initiate infection in porcine ileal explants. Arch. Virol. 101:3547.
56. Heinz, B. A.,, D. O. Cliver,, and B. Donohoe. 1987. Enterovirus replication in porcine ileal expiants. J. Gen. Virol. 68:24952499.
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. 69:67206728.
58. Hewat, E. A.,, T. C. Marlovits,, and D. Blaas. 1998. Structure of a neutralizing antibody bound monovalently to human rhinovirus 2. J. Virol. 72:43964402.
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 9:3942.
60. Hogle, J. M.,, and D. J. Filman. 1989. The antigenic structure of poliovirus. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 323:467478.
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 43:12601266.
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. 31:10831087.
63. Huber, S. A. 1997. Coxsackievirus-induced myocarditis is dependent on distinct immunopathogenic responses in different strains of mice. Lab. Invest. 76:691701.
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. 887:181190.
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. 156:35283534.
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. 51:3580.
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. 141:32143219.
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. 126:13361340.
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. 98:681694.
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. 116:2129.
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 91:55435547.
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. 70:30393044.
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. 68:51265132.
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. 88:6778.
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. 68:195206.
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): 1819.
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. 44:353361.
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. 35:137144.
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. 50:357367.
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. 89:283292.
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 89:28362842.
82. Knowlton, K. U.,, and C. Badorff. 1999. The immune system in viral myocarditis: maintaining the balance. Circ. Res. 85:559561.
83. Kutubuddin, M.,, J. Simons,, and M. Chow. 1992. Identification of T-helper epitopes in the VP1 capsid protein of poliovirus. J. Virol. 66:30423047.
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. 136:219233.
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. 175:11231129.
86. Lanier, L. L. 1998. NK cell receptors. Annu. Rev. Immunol. 16:359393.
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. 65:711718.
88. Leipner, C.,, M. Borchers,, I. Merkle,, and A. Stelzner. 1999. Coxsackievirus B3-induced myocarditis in MHC class II-deficient mice. J. Hum. Virol. 2:102114.
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. 2:191203.
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):2527.
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. 104:398405.
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 98:777785.
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 20:7382.
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. 66:70127020.
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):4965.
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 94:46044609.
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. 291351. 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. 38:124.
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. 56:651654.
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. 34:139151.
101. Mertens, T.,, U. Pika,, and H. J. Eggers. 1983. Cross antigenicity among enteroviruses as revealed by immunoblot technique. Virology 129:431442.
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. 67:12831291.
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. 12:266270.
104. Mondino, A.,, A. Khoruts,, and M. K. Jenkins. 1996. The anatomy of T-cell activation and tolerance. Proc. Natl. Acad. Sci. USA 93:22452252.
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 3:653667.
106. Muckelbauer, J. K.,, and M. G. Rossmann. 1997. The structure of coxsackievirus B3. Curr. Top Microbiol. Immunol. 223:191208.
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 1:804807.
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 76:243249.
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):117120.
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. 145:40944100.
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. 68:181190.
112. Neutra, M. R.,, A. Frey,, and J. P. Kraehenbuhl. 1996. Epithelial M cells: gateways for mucosal infection and immunization. Cell 86:345348.
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. 85:551558.
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. 62:17811794.
115. Parker, D. C. 1993. T cell-dependent B cell activation. Annu. Rev. Immunol. 11:331360.
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 29:143155.
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. 79:22492253.
118. Ramsingh, A.,, N. Chapman,, and S. Tracy. 1997. Coxsackieviruses and diabetes. Bioessays 19:793800.
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. 73:30803086.
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. 14:347358.
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) 95:469481.
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. 65:34753480.
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. 166:8091.
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. 65:47354740.
125. Romagnani, S. 1996. Thl and Th2 in human diseases. Clin. Immunol. Immunopathol. 80:225235.
126. Romero, J. R.,, C. Price,, and J. J. Dunn. 1997. Genetic divergence among the group B coxsackieviruses. Curr. Top. Microbiol. Immunol. 223:97152.
127. Rose, N. R.,, and S. L. Hill. 1996. The pathogenesis of postinfectious myocarditis. Clin. Immunol. Immunopathol. 80:S92S99.
128. Rose, N. R.,, and S. L. Hill. 1996. Autoimmune myocarditis. Int. J. Cardiol. 54:171175.
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 317:145153.
130. Samuelson, A.,, M. Forsgren,, B. Johansson,, B. Wahren,, and M. Sallberg. 1994. Molecular basis for serological cross-reactivity between enteroviruses. Diagn. Lab Immunol. 1:336341.
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. 75:29112924.
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. 427:503509.
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 40:332338.
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. 8:341348.
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. 65:11971201.
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. 17:603617.
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. 54:117125.
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. 223:283303.
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. 216:5256.
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. 96:10351041.
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. 82:613618.
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. 83:463469.
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. 183:105108.
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. 67:360367.
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 89:21702175.
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. 178:330334.
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. 57:246257.
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. 151:39023913.
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 98:5658.
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. 115:236247.
151. Smith, S. C.,, and P. M. Men. 1991. Myosin-induced acute myocarditis is a T cell-mediated disease. J. Immunol. 147:21412147.
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 92:16041611.
153. Tilzey, A. J.,, M. Signy,, and J. E. Banatvala. 1986. Persistent coxsackie B virus specific IgM response in patients with recurrent pericarditis. Lancet 1:14911492.
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 31:496499.
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 37:289303.
156. Tracy, S.,, N. M. Chapman,, R. Rubocki,, and M. Beck,. 1995. The host immune response to enterovirus infections, p. 175191. 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. 62:7081.
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. 69:46074618.
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. 73:13791386.
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 41:4046.
161. Vuorinen, T.,, R. Vainionpaa,, H. Kettinen,, and T. Hyypia. 1994. Coxsackievirus B3 infection in human leukocytes and lymphoid cell lines. Blood 84:823829.
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. 70:90189023.
163. Vuorinen, T.,, R. Vainionpaa,, J. Heino,, and T. Hyypia. 1999. Enterovirus receptors and virus replication in human leukocytes. J. Gen. Virol. 80:921927.
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. 13:115119.
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. 136:18461852.
166. Woodruff, J.F. 1980. Viral myocarditis. A review. Am. J. Pathol. 101:425484.
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. 300:11731179.
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 1:146150.
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. 80:499506.
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 212:614621.
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 95:24692474.
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. 150:21972207.
173. Zinkernagel, R. M., 1997. Virus-induced immunopathology, p. 163180. In N. Nathanson (ed.), Viral Pathogenesis. Lippincott-Raven, Philadelphia, Pa.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error