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Rapid genomic evolution of a non-virulent Coxsackievirus B3 in selenium-deficient mice results in selection of identical virulent isolates

Nature Medicine volume 1, pages 433–436 (1995)Cite this article

Abstract

Previous work from our laboratory demonstrated that selenium deficiency in the mouse allows a normally benign (amyocarditic) cloned and sequenced Coxsackievirus to cause significant heart damage. Furthermore, Coxsackievirus recovered from the hearts of selenium-deficient mice inoculated into selenium-adequate mice still induced significant heart damage, suggesting that the amyocarditic Coxsackievirus had mutated to a virulent phenotype. Here we report that sequence analysis revealed six nucleotide changes between the virulent virus recovered from the selenium-deficient host and the avirulent input virus. These nucleotide changes are consistent with known differences in base composition between virulent and avirulent strains of Coxsackievirus. To the best of our knowledge, this is the first report of a specific nutritional deficiency driving changes in a viral genome, permitting an avirulent virus to acquire virulence due to genetic mutation.

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References

  1. Woodruff, J.F. Viral myocarditis: A review. Am. J. Pathol. 101, 426–482 (1980).

    Google Scholar 

  2. O'Connell, J. & Robinson, J. Coxsackie viral myocarditis. Postgrad. Med. J. 61, 1127–1131 (1985).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  4. Gu, B.Q. Pathology of Keshan disease. A comprehensive review. Chin. Med. J. 96, 251–261 (1983).

    CAS  PubMed  Google Scholar 

  5. Su, C. Preliminary results of viral etiology of Keshan disease. Chin. Med. J. 59, 466–472 (1979).

    Google Scholar 

  6. Bai, J., Wu, S., Ge, K., Deng, X. & Su, C. The combined effect of selenium deficiency and viral infection on the myocardium of mice. Acta Acad. Med. Sin. 2, 29–31 (1984).

    Google Scholar 

  7. Beck, M.A. et al. Amyocarditic Coxsackievirus becomes myocarditic in selenium deficient mice. J. med. Virol. 43, 166–170 (1994).

    Article  CAS  Google Scholar 

  8. Levander, O.A. Considerations on the assessment of selenium status. Fedn Proc. 44, 2579–2583 (1985).

    CAS  Google Scholar 

  9. Klump, W.M., Bergmann, I., Muller, B.C., Ameis, D. & Kandolf, R. Complete nucleotide sequence of infectious Coxsackievirus B3 cDNA: Two initial 5′ uridine residues are regained during plus-strand RNA synthesis. J. Virol. 64, 1573–1580 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Tracy, S., Chapman, N. & Tu, Z. Coxsackievirus B3 from an infectious cDNA copy of the genome is cardiovirulent in mice. Arch. Virol. 122, 399–409 (1993).

    Article  Google Scholar 

  11. Chapman, N.M., Tu, Z., Tracy, S. & Gauntt, C. J. An infectious cDNA copy of the genome of a non-cardiovirulent Coxsackievirus B3 strain—its complete sequence analysis and comparison to the genomes of cardiovirulent Coxsackieviruses. Arch. Virol. 135, 115–130 (1994).

    Article  CAS  Google Scholar 

  12. Holland, J. et al. Rapid evolution of RNA genomes. Science 215, 1577–1585 (1982).

    Article  CAS  Google Scholar 

  13. Minor, P.D., Ferguson, M. & Icenogle, J.P. Antigenic and molecular evolution of the vaccine strain of type 3 poliovirus during the period of excretion by a primary vaccinee. J. gen. Virol. 67, 693–706 (1986).

    Article  CAS  Google Scholar 

  14. Burk, R.F. & Hill, K.E. Selenoprotein P. A selenium-rich extracellular glycoprotein. J. Nutr. 124, 1891–1897 (1994).

    Article  CAS  Google Scholar 

  15. Ames, B.N., Shigenaga, M.K. & Hagen, T.M. Oxidants, antioxidants and the degenerative diseases of aging. Proc. natn Acad. Sci. U.S.A. 90, 7915–7922 (1993).

    Article  CAS  Google Scholar 

  16. Hall, B.G. Spontaneous point mutations that occur more often when advantageous than when neutral. Genetics 126, 5–16 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Caggana, M., Chan, P. & Ramsingh, A. Identification of a single amino acid residue in the capsid protein VP1 of Coxsackievirus B4 that determines the virulent phenotype. J. Virol. 67, 4797–4803 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Almond, J. The attenuation of poliovirus neurovirulence. Annu. Rev. Microbiol. 41, 153–180 (1987).

    Article  CAS  Google Scholar 

  19. Macadam, A.J., Ferguson, G., Arnold, C. & Minor, P.D. An assembly defect as a result of an attenuating mutation in the capsid proteins of the poliovirus type 3 vaccine strain. J. Virol. 65, 5225–5231 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Minor, P.D. et al. The temperature sensitivity and structural effects of a mutation in the capsid protein VP3. J. gen. Virol. 70, 1117–1123 (1989).

    Article  CAS  Google Scholar 

  21. Zhang, H.Y. et al. Attenuation of a reactivated cardiovirulent Coxsackievirus B3: The 5′ nontranslated region does not contain major attenuation determinants. J. med. Virol. 41, 129–137 (1993).

    Article  CAS  Google Scholar 

  22. Vanderpas, J.B. et al. Iodine and selenium deficiency associated with cretinism in northern Zaire. Am. J. clin. Nutr. 52, 1087–1093 (1990).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Frank Porter Graham Child Development Center, CB #8180, University of North Carolina at Chapel Hill, 105 Smith Level Road, Chapel Hill, NC, 27599-8180, USA

    Melinda A. Beck & Qing Shi

  2. Nutrient Requirements and Functions Laboratory, United States Department of Agriculture, Agricultural Research Service, Beltsville Human Nutrition Research Center, Building 307, Room 220, Beltsville, MD, 20705, USA

    Virginia C. Morris & Orville A. Levander

Authors
  1. Melinda A. Beck
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  2. Qing Shi
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  3. Virginia C. Morris
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  4. Orville A. Levander
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Beck, M., Shi, Q., Morris, V. et al. Rapid genomic evolution of a non-virulent Coxsackievirus B3 in selenium-deficient mice results in selection of identical virulent isolates. Nat Med 1, 433–436 (1995). https://doi.org/10.1038/nm0595-433

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