Skip to main content
Log in

Effect of gold(I) compounds on the virulence of an amyocarditic strain of coxsackievirus B3

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Coxsackieviruses, especially B strains (CVB), are known etiological agents of myocarditis. Both amyocardititc and myocarditic strains exist and at least one amyocarditic strain, CVB3/0, can convert to virulence when passaged through selenium or vitamin E-deficient mice. Gold(I)-containing compounds, such as aurothiomalate (ATM) and aurothioglucose (ATG), can act as selenium antagonists. In this study, we examined the effect of intraperitoneal administration of equal doses of ATM or ATG on the virulence of CVB3/0. ATM but not ATG increased mortality in CVB3/0-infected mice. CVB3/0-infected mice treated with ATM had total necrosis of the pancreatic exocrine tissue. Heart damage also occurred in ATM-treated mice but did not correlate with mortality. Increased viral titers and persistence were observed in ATM-treated mice and, to a lesser extent, in ATG-treated mice. Thus, under our conditions, only ATM increased the virulence of CVB3/0, whereas ATG did not. On the other hand, both ATG and ATM inhibited thioredoxin reductase activity in heart and pancreas, but neither affected glutathione peroxidase activity. In contrast, dietary selenium deficiency reduces both enzyme activities. Thus, it is unlikely that these compounds affect virulence by acting as selenium antagonists.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. G. Q. Yang, Keshan disease: an endemic selenium-related deficiency disease, in Trace Elements in Nutrition of Children, R. K. Chandra, ed., Raven, New York, pp. 273–290 (1985).

    Google Scholar 

  2. G. Q. Yang, J. Chen, Z. Wen, K. Ge, L. Zhu, J. Chen, et al., The role of selenium in Keshan disease, Adv. Nutr. Res. 9, 203–231 (1984).

    Google Scholar 

  3. G. Q. Yang, K. Ge, J. Chen, and X. Chen, Selenium-related endemic diseases and the daily selenium requirement of humans, World Rev. Nutr. Diet 55, 98–152 (1988).

    PubMed  CAS  Google Scholar 

  4. T. Peng, Y. Li, Y. Yang, C. Niu, P. Morgan-Capner, L. C. Archard, et al., Characterization of enterovirus isolates from patients with heart muscle disease in a selenium-deficient area of China, J. Clin. Microbiol. 38, 3538–3543 (2000).

    PubMed  CAS  Google Scholar 

  5. M. A. Beck, P. C. Kolbeck, L. H. Rohr, Q. Shi, V. C. Morris, and O. A. Levander, Benign human enterovirus becomes virulent in selenium-deficient mice, J. Med. Virol. 43, 166–170 (1994).

    Article  PubMed  CAS  Google Scholar 

  6. M. A. Beck, P. C. Kolbeck, L. H. Rohr, Q. Shi, V. C. Morris, and O. A. Levander, Vitamin E deficiency intensifies the myocardial injury of coxsackievirus B3 infection of mice, J. Nutr. 124, 345–358 (1994).

    PubMed  CAS  Google Scholar 

  7. M. A. Beck, Q. Shi, V. C. Morris, and O. A. Levander, Rapid genomic evolution of a nonvirulent coxsackievirus B3 in selenium-deficient mice results in selection of identical virulent isolates. Nature Med. 1, 433–436 (1995).

    Article  PubMed  CAS  Google Scholar 

  8. M. A. Beck, R. S. Esworthy, Y.-S. Ho, and F.-F. Chu, Glutathione peroxidase protects mice from viral-induced myocarditis, FASEB J. 12, 1143–1149 (1998).

    PubMed  CAS  Google Scholar 

  9. J. Chaudiere and A. L. Tappel, Interaction of gold (I) with the active site of selenium-glutathione peroxidase, J. Inorg. Biochem. 20, 313–325 (1984).

    Article  PubMed  CAS  Google Scholar 

  10. M. J. Berry, J. D. Kedffer, J. W. Harney, and P. R. Larsen, Selenocysteine confers the biochemical peoperties characteristic of the type I iodothyronine deiodinase. J. Biol. Chem. 266, 14,155–14,158 (1991).

    CAS  Google Scholar 

  11. D. Salvatore, T. Bartha, J. W. Harney, and P. R. Larsen, Molecular biological and biochemical characterization of the human type 2 selenodeiodinase, Endocrinology 137, 3308–3315 (1996).

    Article  PubMed  CAS  Google Scholar 

  12. K. E. Hill, G. W. McCollum, and R. F. Burk, Determination of thioredoxin reductase activity in rat liver supernatant, Anal. Biochem. 253, 123–125 (1997).

    Article  PubMed  CAS  Google Scholar 

  13. M-L. Hu, C. J. Dillard, and A. L. Tappel, Aurothioglucose effect on sulfhydryls and glutathione-metabolizing enzymes: in vivo inhibition of selenium-dependent glutathione peroxidase, Res. Commun Chem. Pathol, Pharm. 59, 147–160 (1988).

    CAS  Google Scholar 

  14. A. D. Smith, C. A. Guidry, V. C. Morris, and O. A. Levander, Aurothioglucose inhibits murine thioredoxin reductase activity in vivo, J. Nutr. 129, 194–198 (1999).

    PubMed  CAS  Google Scholar 

  15. D. Koštová and E. Michnová, The effects of gold thioglucose on peroxidative processes in mice, Physiol. Res. 48, 79–81 (1999).

    PubMed  Google Scholar 

  16. J. Reglinski, D. E. Paterson, S. Latimer, J. M. Campbell, R. Wilson, D. Porter, et al., Myocrisin-mediated oxidative stress, Clin. Chem. Acta 268, 85–99 (1997).

    Article  CAS  Google Scholar 

  17. K. Allner, C. J. Bradish, R. Fitzgeorge, and N. Nathanson, Modfication by sodium aurothiomalate of the expression of virulence in mice by defined stains of Semliki Forest virus, J. Gen. Virol. 24, 221–228 (1974).

    PubMed  CAS  Google Scholar 

  18. N. Stebbing, K. M. Dawson, and I. J. D. Lindley, Requirement for macrophages for interferon to be effective against encephalomyocarditis virus infection of mice, Infect. Immun. 19, 5–11 (1978).

    PubMed  CAS  Google Scholar 

  19. M. Kabiri, E. Basiri, and D. Kadivar, Potentiation of coxsackievirus B3 infection in adult mice pretreated with a gold salt, J. Med. Virol. 3, 125–136 (1978).

    Article  PubMed  CAS  Google Scholar 

  20. S. Mehta and H. E. Webb, The effect of gold sodium thiomulate in adult Swiss/A2G mice infected with togaviruses and flaviviruses, J. Gen. Virol. 68, 2665–2668 (1987).

    PubMed  CAS  Google Scholar 

  21. S. Mehta and H. E. Webb, The effect of gold sodium thiomalate and its constituent part, thiomalate, on the virus titers and the lysosomal enzyme activity in peritoneal macrophages of Swiss/A2G mice infected with the avirulent strain of Semliki Forest virus, J. Exp. Pathol. 71, 359–366 (1990).

    CAS  Google Scholar 

  22. C. A. Gibson, M. R. Wills, E. A. Gould, P. G. Sanders, and A. D. T. Barrett, Effect of administration of sodium aurothiomalate on the virulence of yellow fever viruses in adult mice, Vaccine 8, 590–594 (1990).

    Article  PubMed  CAS  Google Scholar 

  23. M. F. Scallian and J. K. Fazakerley, Aurothiolates enhance the replication of Semliki Forest virus in the CNS and the exocrine pancreas, J. Neuro Virol. 15, 392–400 (1999).

    Google Scholar 

  24. P. K. Smith, R. I. Krohn, G. T. Hermanson, A. K. Mallia, F. H. Gartner, M. D. Provenzano, et al., Measurement of protein using bicinchoninic acid, Anal. Biochem. 150, 76–85 (1985).

    Article  PubMed  CAS  Google Scholar 

  25. A. D. Smith, V. C. Morris, and O. A. Levander, Rapid determination of glutathione peroxidase and thioredoxin reductase activities using a 96-well microplate format: comparison to standard cuvette-based assays, Int. J. Vitam. Nutr. Res. 71, 87–92 (2001).

    Article  PubMed  CAS  Google Scholar 

  26. C. J. Gauntt, M. D. Trousdale, D. R. LaBadie, R. E. Paque, and T. Nealon, Properties of coxsackievirus B3 variants which are amyocarditic or myocarditic for mice, J. Med. Virol. 3, 207–220 (1979).

    Article  PubMed  CAS  Google Scholar 

  27. N. M. Chapman, Z. Tu, S. Tracy, and C. J. Gauntt, An infectious cDNA copy of the genome of a non-cardioivirulent coxsackievirus B3 strain: Its complete sequence analysis and comparison to the genomes of cardiovirulent coxsackieviruses, Arch. Virol. 135, 115–130 (1994).

    Article  PubMed  CAS  Google Scholar 

  28. J-W. Yoon, T. Onodera, and A. L. Notkins, Virus-induced diabetes mellitus XV. Beta cell damage and insulin-dependent hyperglycemia in mice infected with coxsackie virus B4, J. Exp. Med. 148, 1068–1080 (1978).

    Article  PubMed  CAS  Google Scholar 

  29. S. Kuno, A. Itagaki, I. Yamazaki, T. Katsumoto, and T. Kurimura, Pathogenicity of newly isolated coxsackievirus B4 for mouse pancreas, Acta Virol. 28, 433–436 (1984).

    PubMed  CAS  Google Scholar 

  30. A. Ramsingh, J. Slack, J. Silkworth, and A. Hixson, 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 (1989).

    Article  PubMed  CAS  Google Scholar 

  31. C. J. Bradish, K. Allner, and R. Fitzgeorge, Immunomodification and the expression of virulence in mice by defined strains of Semliki Forest virus: the effects of myocrysin and I-asparaginase, J. Gen. Virol. 28, 239–250 (1975).

    Article  PubMed  CAS  Google Scholar 

  32. L. H. Chow, C. J. Gauntt, and B. M. McManus, Differential effects of myocarditic variants of coxsackievirus B3 in inbred mice. A pathlogic characterization of heart tissue damage, Lab. Invest. 64, 55–64 (1991).

    PubMed  CAS  Google Scholar 

  33. R. Blay, K. Simpson, K. Leslie, and S. Huber, Coxsackievirus-induced disease. CD4+ cells initiate both myocarditis and pancreatitis in DBA/2 mice, Am. J. Pathol. 135, 899–907 (1989).

    PubMed  CAS  Google Scholar 

  34. R. M. Gomez, E. F. Lascano, and M. I. Berria, Murine acinar pancreatitis preceding necrotizing myocarditis after coxsackievirus B3 incoculation, J. Med. Virol. 35, 71–75 (1991).

    Article  PubMed  CAS  Google Scholar 

  35. R. M. Gomez, X. Cui, C. G. Castagnino, and M. I. Berria, Differential behaviour in pancreas and heart of two coxsackievirus B3 variants, Intervirology 36, 153–160 (1993).

    PubMed  CAS  Google Scholar 

  36. S. Tracy, K. Hofling, S. Pirruccello, P. H. Lane, S. M. Reyna, and C. J. Gauntt, Group B coxsackievirus myocarditis and pancreatitis: connection between viral virulence phenotypes in mice, J. Med. Virol. 62, 70–81 (2000).

    Article  PubMed  CAS  Google Scholar 

  37. T. M. Szopa, T. Ward, D. M. Dronfield, N. D. Portwood, and K. W. Taylor, Coxsackie B4 viruses with the potential to damage beta cells of the islets are present in clinical isolates, Diabetologia 33, 325–358 (1990).

    Article  PubMed  CAS  Google Scholar 

  38. O. A. Levander, D. P. DeLoach, V. C. Morris, and P. B. Moser, Platelet glutathione peroxidase activity as an index of selenium status in rats, J. Nutr. 113, 55–63 (1983).

    PubMed  CAS  Google Scholar 

  39. R. M. Turkall, G. A. Warr, and M. F. Tsan, Effect of in vivo administration of gold sodium thiomalate on rat macrophage function, Agents Actions 12, 489–498 (1982).

    Article  PubMed  CAS  Google Scholar 

  40. M. Harth, G. A. McCain, and K. Cousin, The modulation of interleukin 1 production by interferon gamma and the inhibitory effects of gold compounds, Immunopharmacology 20, 125–134 (1990).

    Article  PubMed  CAS  Google Scholar 

  41. D. H. Williams, L. J. Jeffery, and E. J. Murray, Aurothioglucose inhibits induced NF-κB and AP-1 activity by acting as an IL-1 functional antagonist, Biochem. Biophys. Acta 1180, 9–14 (1992).

    PubMed  CAS  Google Scholar 

  42. K. Hashimoto, C. E. Whitehurst, and P. E. Lipsky, Synergistic inhibition of T cell proliferation by gold sodium thiomalate and auranofin, J. Rheumatol. 21, 1020–1026 (1994).

    PubMed  CAS  Google Scholar 

  43. P. Barrera, A. M. Th. Boerbooms, L. B. A. van de Putte, and J. W. M. van der Meer, Effects of antirheumatic agents on cytokines. Semin Arthritis Rheumat. 25, 234–253 (1996).

    Article  CAS  Google Scholar 

  44. K. E. Traber, H. Okamoto, C. Kurono, M. Baba, C. Saliou, T. Soji, et al., Anti-rheumatic compound aurothioglucose inhibits tumor necrosis factor-alpha-induced HIV-1 replication in latently infected OM10.1 and Ach2 cells, Int. Immunol. 11, 143–150 (1999).

    Article  PubMed  CAS  Google Scholar 

  45. S. Yoshida, T. Kato, S. Sakurada, C. Kurnon, J. P. Yang, N. Matsui, et al., Inhibition of IL-6 and IL-8 induction from cultured rheumatoid synovial fibroblasts by treatment with aurothioglucose, Int. Immunol. 11, 151–158 (1999).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Smith, A.D., South, P.K. & Levander, O.A. Effect of gold(I) compounds on the virulence of an amyocarditic strain of coxsackievirus B3. Biol Trace Elem Res 84, 67–80 (2001). https://doi.org/10.1385/BTER:84:1-3:067

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1385/BTER:84:1-3:067

Index Entries

Navigation