Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1990 Mar;136(3):669–681.

Secondary enterovirus infection in the murine model of myocarditis. Pathologic and immunologic aspects.

M A Beck 1, N M Chapman 1, B M McManus 1, J C Mullican 1, S Tracy 1
PMCID: PMC1877489  PMID: 2156432

Abstract

Enteroviruses are implicated as etiologic agents in the inflammatory diseases myocarditis and polymyositis. In this report, we show that a previous enterovirus exposure in mice can influence development of myocardial inflammation with a second enteroviral exposure. Inoculation of 25-day-old male C3H/HeJ mice with 10(3) or 10(5) plaque-forming units (PFU) of infectious or ultra violet (UV)-inactivated coxsackievirus B2 (CVB2), followed by inoculation 28 days later with 10(5) PFU of a myocarditic variant of coxsackievirus B3 (CVB3-m) results in more intense myocardial inflammation and injury than is seen in age-matched mice inoculated with CVB3-m alone. More severe disease occurs with the lower primary dose of CVB2. Neutralizing antibody to CVB2 is detected early after primary inoculation and neutralizing antibody to CVB3 is first detected 5 days after secondary inoculation. In vitro proliferation of splenocytes from mice inoculated with one or both viruses occurs in response to both CVB2 and CVB3 antigens. We recently demonstrated that murine T cells are capable of recognizing an enterovirus group antigen. Thus cell-mediated immune responses to a conserved antigenic epitope(s) among the enteroviruses may be involved in the exacerbation of myocardial inflammatory disease during a second enterovirus infection. The secondary infection model described here may more accurately mirror virus-induced myocarditis in the human population because the majority of adults have been exposed to several enteroviruses before induction of disease.

Full text

PDF
669

Images in this article

672Figure 2
on p.672
672Figure 3
on p.672
674Figure 4
on p.674
675Figure 5
on p.675
676Figure 6
on p.676

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bell E. J., McCartney R. A. A study of Coxsackie B virus infections, 1972-1983. J Hyg (Lond) 1984 Oct;93(2):197–203. doi: 10.1017/s0022172400064718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bowles N. E., Richardson P. J., Olsen E. G., Archard L. C. Detection of Coxsackie-B-virus-specific RNA sequences in myocardial biopsy samples from patients with myocarditis and dilated cardiomyopathy. Lancet. 1986 May 17;1(8490):1120–1123. doi: 10.1016/s0140-6736(86)91837-4. [DOI] [PubMed] [Google Scholar]
  3. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  4. Couch R. B., Kasel J. A. Immunity to influenza in man. Annu Rev Microbiol. 1983;37:529–549. doi: 10.1146/annurev.mi.37.100183.002525. [DOI] [PubMed] [Google Scholar]
  5. Easton A. J., Eglin R. P. The detection of coxsackievirus RNA in cardiac tissue by in situ hybridization. J Gen Virol. 1988 Feb;69(Pt 2):285–291. doi: 10.1099/0022-1317-69-2-285. [DOI] [PubMed] [Google Scholar]
  6. Gauntt C. J., Paque R. E., Trousdale M. D., Gudvangen R. J., Barr D. T., Lipotich G. J., Nealon T. J., Duffey P. S. Temperature-sensitive mutant of coxsackievirus B3 establishes resistance in neonatal mice that protects them during adolescence against coxsackievirus B3-induced myocarditis. Infect Immun. 1983 Feb;39(2):851–864. doi: 10.1128/iai.39.2.851-864.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gauntt C. J., Trousdale M. D., LaBadie D. R., Paque R. E., Nealon T. Properties of coxsackievirus B3 variants which are amyocarditic or myocarditic for mice. J Med Virol. 1979;3(3):207–220. doi: 10.1002/jmv.1890030307. [DOI] [PubMed] [Google Scholar]
  8. Godeny E. K., Gauntt C. J. In situ immune autoradiographic identification of cells in heart tissues of mice with coxsackievirus B3-induced myocarditis. Am J Pathol. 1987 Nov;129(2):267–276. [PMC free article] [PubMed] [Google Scholar]
  9. Grist N. R., Bell E. J., Assaad F. Enteroviruses in human disease. Prog Med Virol. 1978;24:114–157. [PubMed] [Google Scholar]
  10. Hashimoto I., Komatsu T. Myocardial changes after infection with Coxsackie virus B3 in nude mice. Br J Exp Pathol. 1978 Feb;59(1):13–20. [PMC free article] [PubMed] [Google Scholar]
  11. Hellman A., Fowler A. K., Steinman H. G., Buzzerd P. M. Studies of the blastogenic response of murine lymphocyte. 3. Specific viral transformation. Proc Soc Exp Biol Med. 1972 Oct;141(1):106–109. doi: 10.3181/00379727-141-36726. [DOI] [PubMed] [Google Scholar]
  12. Hori H., Matoba T., Shingu M., Toshima H. The role of cell mediated immunity in coxsackie B viral myocarditis. Jpn Circ J. 1981 Dec;45(12):1409–1414. doi: 10.1253/jcj.45.1409. [DOI] [PubMed] [Google Scholar]
  13. Horohov D. W., Moore R. N., Rouse B. T. Production of soluble suppressor factors by herpes simplex virus-stimulated splenocytes from herpes simplex virus-immune mice. J Virol. 1985 Jun;54(3):798–803. doi: 10.1128/jvi.54.3.798-803.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Huber S. A., Weller A., Herzum M., Lodge P. A., Estrin M., Simpson K., Guthrie M. Immunopathogenic mechanisms in experimental picornavirus-induced autoimmunity. Pathol Immunopathol Res. 1988;7(4):279–291. doi: 10.1159/000157123. [DOI] [PubMed] [Google Scholar]
  15. Kawai C., Matsumori A., Kumagai N., Tokuda M. Experimental Coxsackie virus B-3 and B-4 myocarditis in mice. Jpn Circ J. 1978 Jan;42(1):43–47. doi: 10.1253/jcj.42.43. [DOI] [PubMed] [Google Scholar]
  16. Kimm S. Y., Ornstein S. M., DeLong E. R., Grufferman S. Secular trends in ischemic heart disease mortality: regional variation. Circulation. 1983 Jul;68(1):3–8. doi: 10.1161/01.cir.68.1.3. [DOI] [PubMed] [Google Scholar]
  17. Lau R. C. Coxsackie B virus infections in New Zealand patients with cardiac and non-cardiac diseases. J Med Virol. 1983;11(2):131–137. doi: 10.1002/jmv.1890110207. [DOI] [PubMed] [Google Scholar]
  18. Lerner A. M., Wilson F. M. Virus myocardiopathy. Prog Med Virol. 1973;15:63–91. [PubMed] [Google Scholar]
  19. Lerner A., Wilson F. M., Reyes M. P. Enteroviruses and the heart (with special emphasis on the probable role of coxsackieviruses, group B, types 1-5). II. Observations in humans. Mod Concepts Cardiovasc Dis. 1975 Mar;44(3):11–15. [PubMed] [Google Scholar]
  20. Orosz C. G., Zinn N. E., Sirinek L., Ferguson R. M. In vivo mechanisms of alloreactivity. I. Frequency of donor-reactive cytotoxic T lymphocytes in sponge matrix allografts. Transplantation. 1986 Jan;41(1):75–83. [PubMed] [Google Scholar]
  21. Reyes M. P., Lerner A. M. Coxsackievirus myocarditis--with special reference to acute and chronic effects. Prog Cardiovasc Dis. 1985 May-Jun;27(6):373–394. doi: 10.1016/0033-0620(85)90001-5. [DOI] [PubMed] [Google Scholar]
  22. Schoub B. D., Johnson S., McAnerney J. M., Dos Santos I. L., Klaassen K. I. Epidemic Coxsackie B virus infection in Johannesburg, South Africa. J Hyg (Lond) 1985 Oct;95(2):447–455. doi: 10.1017/s0022172400062872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tilzey A. J., Signy M., Banatvala J. E. Persistent coxsackie B virus specific IgM response in patients with recurrent pericarditis. Lancet. 1986 Jun 28;1(8496):1491–1492. doi: 10.1016/s0140-6736(86)91519-9. [DOI] [PubMed] [Google Scholar]
  24. Trousdale M. D., Paque R. E., Gauntt C. J. Isolation of Coxsackievirus B3 temperture-sensitive mutants and their assignment to complementation groups. Biochem Biophys Res Commun. 1976 May 23;76(2):368–375. doi: 10.1016/0006-291x(77)90734-3. [DOI] [PubMed] [Google Scholar]
  25. Whitaker J. N. Inflammatory myopathy: a review of etiologic and pathogenetic factors. Muscle Nerve. 1982 Oct;5(8):573–592. doi: 10.1002/mus.880050802. [DOI] [PubMed] [Google Scholar]
  26. Woodruff J. F. Viral myocarditis. A review. Am J Pathol. 1980 Nov;101(2):425–484. [PMC free article] [PubMed] [Google Scholar]
  27. el-Khatib M. R., Chason J. L., Ho K. L., Silberberg B., Lerner A. M. Coxsackievirus B4 myocarditis in mice: valvular changes in virus-infected and control animals. J Infect Dis. 1978 Apr;137(4):410–420. doi: 10.1093/infdis/137.4.410. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES