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. 1985 Feb;27(2):184–191. doi: 10.1128/aac.27.2.184

Antimyocarditic activity of the guanine derivative BIOLF-70 in a coxsackievirus B3 murine model.

C J Gauntt, H M Arizpe, J T Kung, K K Ogilvie, U O Cheriyan
PMCID: PMC176235  PMID: 2580480

Abstract

Prophylactic administration of a nontoxic dose of 9-[[2-benzyloxyl-1-(benzyloxymethyl)ethoxy]methyl]-6-chlo roguanine (BIOLF-70) to mice reduced the number of myocarditic lesions induced by coxsackievirus B3 (CVB3). BIOLF-70 exhibited minimal antiviral activity against CVB3 in HeLa cells and murine neonatal skin fibroblasts and minimally reduced CVB3 yields in heart tissues. The drug had no effect on serum anti-CVB3 neutralizing antibody titers and did not induce the production of interferon. Flow microfluorometric analyses of splenic lymphocytes taken from BIOLF-70-treated, CVB3-inoculated mice at 7 days postinoculation showed that the proportion of T lymphocytes was increased, as measured by fluorescent staining of Thy-1 and Lyt-2 surface markers, compared with the proportion of T lymphocytes in splenic cells from virus-inoculated or BIOLF-70-treated or normal groups of mice. Splenic lymphocytes from BIOLF-70-treated, CVB3-inoculated mice showed reduced cytotoxic activity against CVB3-infected target fibroblasts. Splenic cells from BIOLF-70-treated, CVB3-inoculated mice had slightly higher natural killer cell activity than did those from the other three groups of mice, which had comparatively similar levels of natural killer cell activity. The data suggest that BIOLF-70 exerts antimyocarditic activity perhaps by some antiviral activity in heart tissues and by immunomodulatory mechanisms which appear to involve T suppressor or T cytotoxic lymphocyte subpopulations and natural killer cells.

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Selected References

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  1. Burch G. E., Giles T. D. The role of viruses in the production of heart disease. Am J Cardiol. 1972 Feb;29(2):231–240. doi: 10.1016/0002-9149(72)90634-0. [DOI] [PubMed] [Google Scholar]
  2. GRODUMS E. I., DEMPSTER G. Myocarditis in experimental Coxsackie B-3 infection. Can J Microbiol. 1959 Dec;5:605–615. doi: 10.1139/m59-074. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. 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]
  5. Gudvangen R. J., Duffey P. S., Paque R. E., Gauntt C. J. Levamisole exacerbates coxsackievirus B3-induced murine myocarditis. Infect Immun. 1983 Sep;41(3):1157–1165. doi: 10.1128/iai.41.3.1157-1165.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Huber S. A., Job L. P., Woodruff J. F. In vitro culture of coxsackievirus group B, type 3 immune spleen cells on infected endothelial cells and biological activity of the cultured cells in vivo. Infect Immun. 1984 Feb;43(2):567–573. doi: 10.1128/iai.43.2.567-573.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Huber S. A., Job L. P., Woodruff J. F. Lysis of infected myofibers by coxsackievirus B-3-immune T lymphocytes. Am J Pathol. 1980 Mar;98(3):681–694. [PMC free article] [PubMed] [Google Scholar]
  8. Huber S. A., Job L. P., Woodruff J. F. Sex-related differences in the pattern of coxsackievirus B-3-induced immune spleen cell cytotoxicity against virus-infected myofibers. Infect Immun. 1981 Apr;32(1):68–73. doi: 10.1128/iai.32.1.68-73.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Johnson R. A., Palacios I. Dilated cardiomyopathies of the adult (second of two parts). N Engl J Med. 1982 Oct 28;307(18):1119–1126. doi: 10.1056/NEJM198210283071804. [DOI] [PubMed] [Google Scholar]
  10. KAPLAN A. S., MELNICK J. L. Oral administration of Coxsackie viruses to newborn and adult mice. Proc Soc Exp Biol Med. 1951 Feb;76(2):312–315. doi: 10.3181/00379727-76-18475. [DOI] [PubMed] [Google Scholar]
  11. KILBOURNE E. D., HORSFALL F. L., Jr Lethal infection with coxsackie virus of adult mice given cortisone. Proc Soc Exp Biol Med. 1951 May;77(1):135–138. doi: 10.3181/00379727-77-18702. [DOI] [PubMed] [Google Scholar]
  12. KILBOURNE E. D., WILSON C. B., PERRIER D. The induction of gross myocardial lesions by a Coxsackie (pleurodynia) virus and cortisone. J Clin Invest. 1956 Apr;35(4):362–370. doi: 10.1172/JCI103286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kung J. T., Sharrow S. O., Ahmed A., Habbersett R., Scher I., Paul W. E. B lymphocyte subpopulation defined by a rat monoclonal antibody, 14G8. J Immunol. 1982 May;128(5):2049–2056. [PubMed] [Google Scholar]
  14. Kung J. T., Sharrow S. O., Sieckmann D. G., Lieberman R., Paul W. E. A mouse IgM allotypic determinant (Igh-6.5) recognized by a monoclonal rat antibody. J Immunol. 1981 Sep;127(3):873–876. [PubMed] [Google Scholar]
  15. Kung J. T., Sharrow S. O., Thomas C. A., Paul W. E. Analysis of B lymphocyte differentiation antigens by flow microfluorometry. Immunol Rev. 1982;69:51–68. doi: 10.1111/j.1600-065x.1983.tb00448.x. [DOI] [PubMed] [Google Scholar]
  16. Lanier L. L., Gutman G. A., Lewis D. E., Griswold S. T., Warner N. L. Monoclonal antibodies against rat immunoglobulin kappa chains. Hybridoma. 1982;1(2):125–131. doi: 10.1089/hyb.1.1982.1.125. [DOI] [PubMed] [Google Scholar]
  17. Ledbetter J. A., Herzenberg L. A. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev. 1979;47:63–90. doi: 10.1111/j.1600-065x.1979.tb00289.x. [DOI] [PubMed] [Google Scholar]
  18. Lerner A. M., Wilson F. M. Virus myocardiopathy. Prog Med Virol. 1973;15:63–91. [PubMed] [Google Scholar]
  19. Levine H. D. Virus myocarditis: a critique of the literature from clinical, electrocardiographic, and pathologic standpoints. Am J Med Sci. 1979 Mar-Apr;277(2):132–143. [PubMed] [Google Scholar]
  20. Lewes D. Viral myocarditis. Practitioner. 1976 Mar;216(1293):281–287. [PubMed] [Google Scholar]
  21. Loken M. R., Herzenber L. A. Analysis of cell populations with a fluorescence-activated cell sorter. Ann N Y Acad Sci. 1975 Jun 30;254:163–171. doi: 10.1111/j.1749-6632.1975.tb29166.x. [DOI] [PubMed] [Google Scholar]
  22. Loria R. M., Kibrick S., Broitman S. A. Peroral infection with group B coxsackievirus in the newborn mouse: a model for human infection. J Infect Dis. 1974 Sep;130(3):225–230. doi: 10.1093/infdis/130.3.225. [DOI] [PubMed] [Google Scholar]
  23. Paque R. E., Gauntt C. J., Nealon T. J. Assessment of cell-mediated immunity against coxsackievirus B3-induced myocarditis in a primate model (Papio papio). Infect Immun. 1981 Jan;31(1):470–479. doi: 10.1128/iai.31.1.470-479.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Paque R. E., Gauntt C. J., Nealon T. J., Trousdale M. D. Assessment of cell-mediated hypersensitivity against coxsackievirus B3 viral-induced myocarditis utilizing hypertonic salt extracts of cardiac tissue. J Immunol. 1978 May;120(5):1672–1678. [PubMed] [Google Scholar]
  25. Paque R. E., Straus D. C., Nealon T. J., Gauntt C. J. Fractionation and immunologic assessment of KCl-extracted cardiac antigens in coxsackievirus B3 virus-induced myocarditis. J Immunol. 1979 Jul;123(1):358–364. [PubMed] [Google Scholar]
  26. Rager-Zisman B., Allison A. C. Effects of immunosuppression on coxsackie B-3 virus infection in mice, and passive protection by circulating antibody. J Gen Virol. 1973 Jun;19(3):339–351. doi: 10.1099/0022-1317-19-3-339. [DOI] [PubMed] [Google Scholar]
  27. Reyes M. P., Ho K. L., Smith F., Lerner A. M. A mouse model of dilated-type cardiomyopathy due to coxsackievirus B3. J Infect Dis. 1981 Sep;144(3):232–236. doi: 10.1093/infdis/144.3.232. [DOI] [PubMed] [Google Scholar]
  28. Sharrow S. O., Ozato K., Sachs D. H. Phenotypic expression of I-A and I-E/C subregion determinants on murine thymocytes. J Immunol. 1980 Nov;125(5):2263–2268. [PubMed] [Google Scholar]
  29. TILLES J. G., ELSON S. H., SHAKA J. A., ABELMANN W. H., LERNER A. M., FINLAND M. EFFECTS OF EXERCISE ON COXSACKIE A9 MYOCARDITIS IN ADULT MICE. Proc Soc Exp Biol Med. 1964 Dec;117:777–782. doi: 10.3181/00379727-117-29696. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Trousdale M. D., Paque R. E., Nealon T., Gauntt C. J. Assessment of coxsackievirus B3 ts mutants for induction of myocarditis in a murine model. Infect Immun. 1979 Feb;23(2):486–495. doi: 10.1128/iai.23.2.486-495.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wong C. Y., Woodruff J. J., Woodruff J. F. Generation of cytotoxic T lymphocytes during coxsackievirus B-3 infection. I. Model and viral specificity1. J Immunol. 1977 Apr;118(4):1159–1164. [PubMed] [Google Scholar]
  33. Wong C. Y., Woodruff J. J., Woodruff J. F. Generation of cytotoxic T lymphocytes during coxsackievirus B-3 infection. III. Role of sex. J Immunol. 1977 Aug;119(2):591–597. [PubMed] [Google Scholar]
  34. Wong C. Y., Woodruff J. J., Woodruff J. F. Generation of cytotoxic T lymphocytes during coxsackievirus tb-3 infection. II. Characterization of effector cells and demonstration cytotoxicity against viral-infected myofibers1. J Immunol. 1977 Apr;118(4):1165–1169. [PubMed] [Google Scholar]
  35. Woodruff J. F., Kilbourne E. D. The influence of quantitated post-weaning undernutrition on coxsackievirus B3 infection of adult mice. I. Viral persistence and increased severity of lesions. J Infect Dis. 1970 Feb;121(2):137–163. doi: 10.1093/infdis/121.2.137. [DOI] [PubMed] [Google Scholar]
  36. Woodruff J. F. Viral myocarditis. A review. Am J Pathol. 1980 Nov;101(2):425–484. [PMC free article] [PubMed] [Google Scholar]
  37. Woodruff J. F., Woodruff J. J. Involvement of T lymphocytes in the pathogenesis of coxsackie virus B3 heart disease. J Immunol. 1974 Dec;113(6):1726–1734. [PubMed] [Google Scholar]

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