1887

Abstract

The foot-and-mouth disease virus (FMDV) capsid protein precursor P1-2A is cleaved by the virus-encoded 3C protease to VP0, VP3, VP1 and 2A. It was shown previously that modification of a single amino acid residue (K210E) within the VP1 protein and close to the VP1/2A cleavage site, inhibited cleavage of this junction and produced ‘self-tagged’ virus particles. A second site substitution (E83K) within VP1 was also observed within the rescued virus [Gullberg (2013). , 11591–11603]. It was shown here that introduction of this E83K change alone into a serotype O virus resulted in the rapid accumulation of a second site substitution within the 2A sequence (L2P), which also blocked VP1/2A cleavage. This suggests a linkage between the E83K change in VP1 and cleavage of the VP1/2A junction. Cells infected with viruses containing the VP1 K210E or the 2A L2P substitutions contained the uncleaved VP1-2A protein. The 2A L2P substitution resulted in the VP1/2A junction being highly resistant to cleavage by the 3C protease, hence it may be a preferred route for ‘tagging’ virus particles.

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2014-11-01
2019-11-15
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References

  1. Belsham G. J.. ( 2005;). Translation and replication of FMDV RNA. . Curr Top Microbiol Immunol 288:, 43–70.[PubMed]
    [Google Scholar]
  2. Birtley J. R., Knox S. R., Jaulent A. M., Brick P., Leatherbarrow R. J., Curry S.. ( 2005;). Crystal structure of foot-and-mouth disease virus 3C protease. New insights into catalytic mechanism and cleavage specificity. . J Biol Chem 280:, 11520–11527. [CrossRef][PubMed]
    [Google Scholar]
  3. Bøtner A., Kakker N. K., Barbezange C., Berryman S., Jackson T., Belsham G. J.. ( 2011;). Capsid proteins from field strains of foot-and-mouth disease virus confer a pathogenic phenotype in cattle on an attenuated, cell-culture-adapted virus. . J Gen Virol 92:, 1141–1151. [CrossRef][PubMed]
    [Google Scholar]
  4. Carrillo C., Tulman E. R., Delhon G., Lu Z., Carreno A., Vagnozzi A., Kutish G. F., Rock D. L.. ( 2005;). Comparative genomics of foot-and-mouth disease virus. . J Virol 79:, 6487–6504. [CrossRef][PubMed]
    [Google Scholar]
  5. Curry S., Abrams C. C., Fry E., Crowther J. C., Belsham G. J., Stuart D. I., King A. M.. ( 1995;). Viral RNA modulates the acid sensitivity of foot-and-mouth disease virus capsids. . J Virol 69:, 430–438.[PubMed]
    [Google Scholar]
  6. Curry S., Roqué-Rosell N., Zunszain P. A., Leatherbarrow R. J.. ( 2007;). Foot-and-mouth disease virus 3C protease: recent structural and functional insights into an antiviral target. . Int J Biochem Cell Biol 39:, 1–6. [CrossRef][PubMed]
    [Google Scholar]
  7. Donnelly M. L., Luke G., Mehrotra A., Li X., Hughes L. E., Gani D., Ryan M. D.. ( 2001;). Analysis of the aphthovirus 2A/2B polyprotein ‘cleavage’ mechanism indicates not a proteolytic reaction, but a novel translational effect: a putative ribosomal ‘skip’. . J Gen Virol 82:, 1013–1025.[PubMed]
    [Google Scholar]
  8. Ellard F. M., Drew J., Blakemore W. E., Stuart D. I., King A. M.. ( 1999;). Evidence for the role of His-142 of protein 1C in the acid-induced disassembly of foot-and-mouth disease virus capsids. . J Gen Virol 80:, 1911–1918.[PubMed]
    [Google Scholar]
  9. Escarmís C., Perales C., Domingo E.. ( 2009;). Biological effect of Muller’s Ratchet: distant capsid site can affect picornavirus protein processing. . J Virol 83:, 6748–6756. [CrossRef][PubMed]
    [Google Scholar]
  10. Geller R., Vignuzzi M., Andino R., Frydman J.. ( 2007;). Evolutionary constraints on chaperone-mediated folding provide an antiviral approach refractory to development of drug resistance. . Genes Dev 21:, 195–205. [CrossRef][PubMed]
    [Google Scholar]
  11. Gullberg M., Muszynski B., Organtini L. J., Ashley R. E., Hafenstein S. L., Belsham G. J., Polacek C.. ( 2013a;). Assembly and characterization of foot-and-mouth disease virus empty capsid particles expressed within mammalian cells. . J Gen Virol 94:, 1769–1779. [CrossRef][PubMed]
    [Google Scholar]
  12. Gullberg M., Polacek C., Bøtner A., Belsham G. J.. ( 2013b;). Processing of the VP1/2A junction is not necessary for production of foot-and-mouth disease virus empty capsids and infectious viruses: characterization of “self-tagged” particles. . J Virol 87:, 11591–11603. [CrossRef][PubMed]
    [Google Scholar]
  13. Logan D., Abu-Ghazaleh R., Blakemore W., Curry S., Jackson T., King A., Lea S., Lewis R., Newman J.. & other authors ( 1993;). Structure of a major immunogenic site on foot-and-mouth disease virus. . Nature 362:, 566–568. [CrossRef][PubMed]
    [Google Scholar]
  14. Maree F. F., Blignaut B., de Beer T. A., Visser N., Rieder E. A.. ( 2010;). Mapping of amino acid residues responsible for adhesion of cell culture-adapted foot-and-mouth disease SAT type viruses. . Virus Res 153:, 82–91. [CrossRef][PubMed]
    [Google Scholar]
  15. Medina M., Domingo E., Brangwyn J. K., Belsham G. J.. ( 1993;). The two species of the foot-and-mouth disease virus leader protein, expressed individually, exhibit the same activities. . Virology 194:, 355–359. [CrossRef][PubMed]
    [Google Scholar]
  16. Nayak A., Goodfellow I. G., Woolaway K. E., Birtley J., Curry S., Belsham G. J.. ( 2006;). Role of RNA structure and RNA binding activity of foot-and-mouth disease virus 3C protein in VPg uridylylation and virus replication. . J Virol 80:, 9865–9875. [CrossRef][PubMed]
    [Google Scholar]
  17. OIE ( 2009;). Foot-and-mouth disease. Manual of standards for diagnostic test and vaccines for terrestrial animals. . http://web.oie.int/eng/normes/MMANUAL/A_Index.htm.
    [Google Scholar]
  18. Pettersen E. F., Goddard T. D., Huang C. C., Couch G. S., Greenblatt D. M., Meng E. C., Ferrin T. E.. ( 2004;). UCSF Chimera–a visualization system for exploratory research and analysis. . J Comput Chem 25:, 1605–1612. [CrossRef][PubMed]
    [Google Scholar]
  19. Polacek C., Gullberg M., Li J., Belsham G. J.. ( 2013;). Low levels of foot-and-mouth disease virus 3C protease expression are required to achieve optimal capsid protein expression and processing in mammalian cells. . J Gen Virol 94:, 1249–1258. [CrossRef][PubMed]
    [Google Scholar]
  20. Reed L. J., Muench H.. ( 1938;). A simple method of estimating fifty percent endpoints. . Am J Hyg 27:, 493–497.
    [Google Scholar]
  21. Roeder P. L., Le Blanc Smith P. M.. ( 1987;). Detection and typing of foot-and-mouth disease virus by enzyme-linked immunosorbent assay: a sensitive, rapid and reliable technique for primary diagnosis. . Res Vet Sci 43:, 225–232.[PubMed]
    [Google Scholar]
  22. Ryan M. D., Belsham G. J., King A. M.. ( 1989;). Specificity of enzyme-substrate interactions in foot-and-mouth disease virus polyprotein processing. . Virology 173:, 35–45. [CrossRef][PubMed]
    [Google Scholar]
  23. Sanner M. F., Olson A. J., Spehner J. C.. ( 1996;). Reduced surface: an efficient way to compute molecular surfaces. . Biopolymers 38:, 305–320. [CrossRef][PubMed]
    [Google Scholar]
  24. Strebel K., Beck E.. ( 1986;). A second protease of foot-and-mouth disease virus. . J Virol 58:, 893–899.[PubMed]
    [Google Scholar]
  25. Thompson J. D., Higgins D. G., Gibson T. J.. ( 1994;). CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. . Nucleic Acids Res 22:, 4673–4680. [CrossRef][PubMed]
    [Google Scholar]
  26. Yang D., Zhang C., Zhao L., Zhou G., Wang H., Yu L.. ( 2011;). Identification of a conserved linear epitope on the VP1 protein of serotype O foot-and-mouth disease virus by neutralising monoclonal antibody 8E8. . Virus Res 155:, 291–299. [CrossRef][PubMed]
    [Google Scholar]
  27. Yu Y., Wang H., Zhao L., Zhang C., Jiang Z., Yu L.. ( 2011;). Fine mapping of a foot-and-mouth disease virus epitope recognized by serotype-independent monoclonal antibody 4B2. . J Microbiol 49:, 94–101. [CrossRef][PubMed]
    [Google Scholar]
  28. Zhao Q., Pacheco J. M., Mason P. W.. ( 2003;). Evaluation of genetically engineered derivatives of a Chinese strain of foot-and-mouth disease virus reveals a novel cell-binding site which functions in cell culture and in animals. . J Virol 77:, 3269–3280. [CrossRef][PubMed]
    [Google Scholar]
  29. Zunszain P. A., Knox S. R., Sweeney T. R., Yang J., Roqué-Rosell N., Belsham G. J., Leatherbarrow R. J., Curry S.. ( 2010;). Insights into cleavage specificity from the crystal structure of foot-and-mouth disease virus 3C protease complexed with a peptide substrate. . J Mol Biol 395:, 375–389. [CrossRef][PubMed]
    [Google Scholar]
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