Cardioviral poly(C) tracts and viral pathogenesis

  • A. C. Palmenberg
  • J. E. Osorio
Conference paper
Part of the Archives of Virology Supplementum book series (ARCHIVES SUPPL, volume 9)


Mengovirus is a prototypical member of the cardiovirus genus of the family Picornaviridae. The positive-strand RNA genome is 7761 bases in length and encodes a polyprotein of 2293 amino acids. The 5′ non-coding region (758 bases) contains an unusual homopolymeric poly(C) tract, which in the wild-type virus, has a sequence of C50UC10. We have discovered through genetic engineering that truncation or deletion of this poly(C) sequence yields infectious virus isolates that grow well in cell culture, but are 106 to 109 fold less pathogenic to mice than the wild type strain. Animals receiving sublethal doses of the short poly(C) strains characteristically develop high levels of neutralizing antibodies and acquire lifelong protective immunity against challenge with wild type virus. Effectively, the genetically engineered strains are superb vaccines against cardio virus disease. Moreover, their potential is not limited to murine hosts. Pigs and sub-human primates have also been protectively vaccinated with short poly(C) tract Mengo viruses. The molecular mechanism of poly(C)-mediated pathogenesis is currently under study. Most hypotheses link the activity to induction of the antiviral cytokine, interferon.


Encephalomyocarditis Virus Short Poly Murine Host Tract Virus Mengo Virus 
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  1. 1.
    Bae YS, Eun HM, Yoon JW (1989) Molecular identification of a diabetogenic viral gene. Diabetes 38: 316–320PubMedCrossRefGoogle Scholar
  2. 2.
    Brown F, Newman JFE, Stott EJ, Porter AG, Frisby D, Newton D, Carey N, Fellner P (1974) Poly C in animal viral RNAs. Nature 251: 342–344PubMedCrossRefGoogle Scholar
  3. 3.
    Callahan PL, Mizutani S, Colonno RJ (1985) Molecular cloning and complete sequence determination of RNA genome of human rhinovirus type 14. Proc Natl Acad Sci USA 82: 732–736PubMedCrossRefGoogle Scholar
  4. 4.
    Cohen SH, Naviaux RK, Brink KMV, Jordan GW (1988) Comparison of the nucleotide sequences of diabetogenic and nondiabetogenic encephalomyocarditis virus. Virology 166: 603–607PubMedCrossRefGoogle Scholar
  5. 5.
    Duke GM, Hoffman MA, Palmenberg AC (1992) Sequence and structural elements that contribute to efficient encephalomyocarditis viral RNA translation. J Virol 66: 1602–1609PubMedGoogle Scholar
  6. 6.
    Duke GM, Osorio JE, Palmenberg AC (1990) Attenuation of Mengovirus through genetic engineering of the 5′ noncoding poly(C) tract. Nature 343: 474–476PubMedCrossRefGoogle Scholar
  7. 7.
    Duke GM, Palmenberg AC (1989) Cloning and synthesis of infectious cardiovirus RNAs containing short, discrete poly(C) tracts. J Virol 63: 1822–1826PubMedGoogle Scholar
  8. 8.
    Escarmis C, Toja M, Medina M, Domingo E (1992) Modifications of the 5′ untranslated region of foot-and-mouth disease virus after prolonged persistence in cell culture. Virus Res 26:113–125PubMedCrossRefGoogle Scholar
  9. 9.
    Giron DJ, Agostini HJ, Thomas DC (1988) Effect of interferons and poly(I): poly(C) on the pathogenesis of the diabetogenic variant of encephalomyocarditis virus in different mouse strains. J Interferon Res 8: 745–753PubMedCrossRefGoogle Scholar
  10. 10.
    Grainer JH (1961) Studies on the natural and experimental infection of animals in Florida with the encephalomyocarditis virus. Proc US Livestock San A: 556–572Google Scholar
  11. 11.
    Helwig FC, Schmidt ECH (1945) A filter passing agent producing intersticial myocarditis in anthropoid apes and small animals. Science 102: 31–33PubMedCrossRefGoogle Scholar
  12. 12.
    Hubbard GB, Soike KF, Butler TM, Carey KD, Davis H, Butcher WI, Gauntt CJ (1992) An encephalomyocarditis virus epizootic in a baboon colony. Lab Anim Sci 42: 233–239PubMedGoogle Scholar
  13. 13.
    Jordan GW, Cohen SH (1987) Encephalomyocarditis virus-induced diabetes mellitus in mice: Model of viral pathogenesis. Rev Infect Dis 9: 917–924Google Scholar
  14. 14.
    Palmenberg AC (1987) Genome organization, translation and processing in picor-naviruses. In: Rolands DJ, Mahy BWJ, Mayo M (eds) The molecular biology of positive strand RNA viruses. Academic Press, London, pp 1–15Google Scholar
  15. 15.
    Palmenberg AC (1989) Sequence alignments of picornaviral capsid proteins. In: Semler B, Semler BL, Ehrenfeld E (eds) Molecular aspects of Picornavirus infection and detection. ASM Publications, Washington, pp 211–241Google Scholar
  16. 16.
    Racaniello VR, Baltimore D (1981) Cloned poliovirus complementary DNA is infectious in mammalian cells. Science 214: 916–918PubMedCrossRefGoogle Scholar
  17. 17.
    Simon EH, Kung S, Koh TT, Brandman P (1976) Interferon sensitive mutants of Mengovirus. I. Isolation and biological characterization. Virology 69: 727–736Google Scholar
  18. 18.
    Zschiesche W, Veckenstedt A (1979) Pathogenicity of Mengo virus to mice. III. Potentiation of infection by immunosuppressants. Exp Pathol 17: 387–393Google Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • A. C. Palmenberg
    • 1
  • J. E. Osorio
    • 1
  1. 1.Institute for Molecular Virology, Department of Animal Health and Biomedical SciencesUniversity of Wisconsin MadisonMadisonUSA

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