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. 1993 Aug;67(8):4797–4803. doi: 10.1128/jvi.67.8.4797-4803.1993

Identification of a single amino acid residue in the capsid protein VP1 of coxsackievirus B4 that determines the virulent phenotype.

M Caggana 1, P Chan 1, A Ramsingh 1
PMCID: PMC237866  PMID: 8392614

Abstract

To identify the molecular determinants of virulence for coxsackievirus B4, a panel of recombinant, chimeric viruses were constructed from cDNA clones of a virulent virus, CB4-V, and a nonvirulent virus, CB4-P. Initial studies mapped a major determinant of virulence to the 5' end of the viral genome, which contained the 5' untranslated and the P1 regions (A. Ramsingh, A. Hixson, B. Duceman, and J. Slack, J. Virol. 64:3078-3081, 1990). To determine whether the 5' untranslated region contributed to the virulent phenotype, a chimeric virus (vCB403) containing this region of the virulent virus on an avirulent background was tested in mice. The vCB403 construct displayed a phenotype similar to that of CB4-P, suggesting that the 5' untranslated region did not significantly contribute to virulence. Analysis of the sequence data of the P1 regions of both CB4-V and CB4-P revealed five mutations that resulted in amino acid substitutions in VP1, VP2, and VP4 (A. Ramsingh, H. Araki, S. Bryant, and A. Hixson, Virus Res. 23:281-292, 1992). Analysis of individual mutations in both VP1 and VP2 revealed that a single residue (Thr-129 of VP1) determined the virulent phenotype.

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Selected References

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  1. Barger M. T., Craighead J. E. Immunomodulation of encephalomyocarditis virus-induced disease in A/J mice. J Virol. 1991 May;65(5):2676–2681. doi: 10.1128/jvi.65.5.2676-2681.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Duke G. M., Osorio J. E., Palmenberg A. C. Attenuation of Mengo virus through genetic engineering of the 5' noncoding poly(C) tract. Nature. 1990 Feb 1;343(6257):474–476. doi: 10.1038/343474a0. [DOI] [PubMed] [Google Scholar]
  3. Fu J. L., Stein S., Rosenstein L., Bodwell T., Routbort M., Semler B. L., Roos R. P. Neurovirulence determinants of genetically engineered Theiler viruses. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4125–4129. doi: 10.1073/pnas.87.11.4125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Grist N. R., Bell E. J., Assaad F. Enteroviruses in human disease. Prog Med Virol. 1978;24:114–157. [PubMed] [Google Scholar]
  5. Hogle J. M., Chow M., Filman D. J. Three-dimensional structure of poliovirus at 2.9 A resolution. Science. 1985 Sep 27;229(4720):1358–1365. doi: 10.1126/science.2994218. [DOI] [PubMed] [Google Scholar]
  6. Jenkins O., Booth J. D., Minor P. D., Almond J. W. The complete nucleotide sequence of coxsackievirus B4 and its comparison to other members of the Picornaviridae. J Gen Virol. 1987 Jul;68(Pt 7):1835–1848. doi: 10.1099/0022-1317-68-7-1835. [DOI] [PubMed] [Google Scholar]
  7. Kawamura N., Kohara M., Abe S., Komatsu T., Tago K., Arita M., Nomoto A. Determinants in the 5' noncoding region of poliovirus Sabin 1 RNA that influence the attenuation phenotype. J Virol. 1989 Mar;63(3):1302–1309. doi: 10.1128/jvi.63.3.1302-1309.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. McMaster G. K., Carmichael G. G. Analysis of single- and double-stranded nucleic acids on polyacrylamide and agarose gels by using glyoxal and acridine orange. Proc Natl Acad Sci U S A. 1977 Nov;74(11):4835–4838. doi: 10.1073/pnas.74.11.4835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. RAABO E., TERKILDSEN T. C. On the enzymatic determination of blood glucose. Scand J Clin Lab Invest. 1960;12(4):402–407. doi: 10.3109/00365516009065404. [DOI] [PubMed] [Google Scholar]
  10. Racaniello V. R., Baltimore D. Cloned poliovirus complementary DNA is infectious in mammalian cells. Science. 1981 Nov 20;214(4523):916–919. doi: 10.1126/science.6272391. [DOI] [PubMed] [Google Scholar]
  11. Ramsingh A., Araki H., Bryant S., Hixson A. Identification of candidate sequences that determine virulence in Coxsackievirus B4. Virus Res. 1992 May;23(3):281–292. doi: 10.1016/0168-1702(92)90114-o. [DOI] [PubMed] [Google Scholar]
  12. Ramsingh A., Hixson A., Duceman B., Slack J. Evidence suggesting that virulence maps to the P1 region of the coxsackievirus B4 genome. J Virol. 1990 Jun;64(6):3078–3081. doi: 10.1128/jvi.64.6.3078-3081.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ramsingh A., Slack J., Silkworth J., Hixson A. Severity of disease induced by a pancreatropic Coxsackie B4 virus correlates with the H-2Kq locus of the major histocompatibility complex. Virus Res. 1989 Dec;14(4):347–358. doi: 10.1016/0168-1702(89)90027-0. [DOI] [PubMed] [Google Scholar]
  14. Ren R. B., Moss E. G., Racaniello V. R. Identification of two determinants that attenuate vaccine-related type 2 poliovirus. J Virol. 1991 Mar;65(3):1377–1382. doi: 10.1128/jvi.65.3.1377-1382.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Saiki R. K., Bugawan T. L., Horn G. T., Mullis K. B., Erlich H. A. Analysis of enzymatically amplified beta-globin and HLA-DQ alpha DNA with allele-specific oligonucleotide probes. Nature. 1986 Nov 13;324(6093):163–166. doi: 10.1038/324163a0. [DOI] [PubMed] [Google Scholar]
  16. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Toyoda H., Kohara M., Kataoka Y., Suganuma T., Omata T., Imura N., Nomoto A. Complete nucleotide sequences of all three poliovirus serotype genomes. Implication for genetic relationship, gene function and antigenic determinants. J Mol Biol. 1984 Apr 25;174(4):561–585. doi: 10.1016/0022-2836(84)90084-6. [DOI] [PubMed] [Google Scholar]
  18. Westrop G. D., Wareham K. A., Evans D. M., Dunn G., Minor P. D., Magrath D. I., Taffs F., Marsden S., Skinner M. A., Schild G. C. Genetic basis of attenuation of the Sabin type 3 oral poliovirus vaccine. J Virol. 1989 Mar;63(3):1338–1344. doi: 10.1128/jvi.63.3.1338-1344.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. van der Werf S., Bradley J., Wimmer E., Studier F. W., Dunn J. J. Synthesis of infectious poliovirus RNA by purified T7 RNA polymerase. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2330–2334. doi: 10.1073/pnas.83.8.2330. [DOI] [PMC free article] [PubMed] [Google Scholar]

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