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. 1988 Jun;62(6):2033–2040. doi: 10.1128/jvi.62.6.2033-2040.1988

Analysis of neutralizing epitopes on foot-and-mouth disease virus.

E Pfaff 1, H J Thiel 1, E Beck 1, K Strohmaier 1, H Schaller 1
PMCID: PMC253288  PMID: 2835507

Abstract

For the investigation of the antigenic determinant structure of foot-and-mouth disease virus (FMDV), neutralizing monoclonal antibodies (MAbs) against complete virus were characterized by Western blot (immunoblot), enzyme immunoassay, and competition experiments with a synthetic peptide, isolated coat protein VP1, and viral particles as antigens. Two of the four MAbs reacted with each of these antigens, while the other two MAbs recognized only complete viral particles and reacted only very poorly with the peptide. The four MAbs showed different neutralization patterns with a panel of 11 different FMDV strains. cDNA-derived VP1 protein sequences of the different strains were compared to find correlations between the primary structure of the protein and the ability of virus to be neutralized. Based on this analysis, it appears that the first two MAbs recognized overlapping sequential epitopes in the known antigenic site represented by the peptide, whereas the two other MAbs recognized conformational epitopes. These conclusions were supported and extended by structural analyses of FMDV mutants resistant to neutralization by an MAb specific for a conformational epitope. These results demonstrate that no amino acid exchanges had occurred in the primary antigenic site of VP1 but instead in the other coat proteins VP2 and VP3, which by themselves do not induce neutralizing antibodies.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bachrach H. L., Moore D. M., McKercher P. D., Polatnick J. Immune and antibody responses to an isolated capsid protein of foot-and-mouth disease virus. J Immunol. 1975 Dec;115(6):1636–1641. [PubMed] [Google Scholar]
  2. Baxt B., Morgan D. O., Robertson B. H., Timpone C. A. Epitopes on foot-and-mouth disease virus outer capsid protein VP1 involved in neutralization and cell attachment. J Virol. 1984 Aug;51(2):298–305. doi: 10.1128/jvi.51.2.298-305.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Beck E., Feil G., Strohmaier K. The molecular basis of the antigenic variation of foot-and-mouth disease virus. EMBO J. 1983;2(4):555–559. doi: 10.1002/j.1460-2075.1983.tb01462.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Beck E., Forss S., Strebel K., Cattaneo R., Feil G. Structure of the FMDV translation initiation site and of the structural proteins. Nucleic Acids Res. 1983 Nov 25;11(22):7873–7885. doi: 10.1093/nar/11.22.7873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Beck E., Strohmaier K. Subtyping of European foot-and-mouth disease virus strains by nucleotide sequence determination. J Virol. 1987 May;61(5):1621–1629. doi: 10.1128/jvi.61.5.1621-1629.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bittle J. L., Houghten R. A., Alexander H., Shinnick T. M., Sutcliffe J. G., Lerner R. A., Rowlands D. J., Brown F. Protection against foot-and-mouth disease by immunization with a chemically synthesized peptide predicted from the viral nucleotide sequence. Nature. 1982 Jul 1;298(5869):30–33. doi: 10.1038/298030a0. [DOI] [PubMed] [Google Scholar]
  7. Blondel B., Crainic R., Fichot O., Dufraisse G., Candrea A., Diamond D., Girard M., Horaud F. Mutations conferring resistance to neutralization with monoclonal antibodies in type 1 poliovirus can be located outside or inside the antibody-binding site. J Virol. 1986 Jan;57(1):81–90. doi: 10.1128/jvi.57.1.81-90.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. DiMarchi R., Brooke G., Gale C., Cracknell V., Doel T., Mowat N. Protection of cattle against foot-and-mouth disease by a synthetic peptide. Science. 1986 May 2;232(4750):639–641. doi: 10.1126/science.3008333. [DOI] [PubMed] [Google Scholar]
  9. Ferguson M., Minor P. D., Magrath D. I., Qui Y. H., Spitz M., Schild G. C. Neutralization epitopes on poliovirus type 3 particles: an analysis using monoclonal antibodies. J Gen Virol. 1984 Jan;65(Pt 1):197–201. doi: 10.1099/0022-1317-65-1-197. [DOI] [PubMed] [Google Scholar]
  10. Geysen H. M., Meloen R. H., Barteling S. J. Use of peptide synthesis to probe viral antigens for epitopes to a resolution of a single amino acid. Proc Natl Acad Sci U S A. 1984 Jul;81(13):3998–4002. doi: 10.1073/pnas.81.13.3998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Grubman M. J., Morgan D. O. Antigenic comparison of foot-and-mouth disease virus serotypes with monoclonal antibodies. Virus Res. 1986 Oct;6(1):33–43. doi: 10.1016/0168-1702(86)90055-9. [DOI] [PubMed] [Google Scholar]
  12. Haresnape J. M., McCahon D. Four independent antigenic determinants on the capsid polypeptides of aphthovirus. J Gen Virol. 1983 Nov;64(Pt 11):2345–2355. doi: 10.1099/0022-1317-64-11-2345. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Küpper H., Keller W., Kurz C., Forss S., Schaller H., Franze R., Strohmaier K., Marquardt O., Zaslavsky V. G., Hofschneider P. H. Cloning of cDNA of major antigen of foot and mouth disease virus and expression in E. coli. Nature. 1981 Feb 12;289(5798):555–559. doi: 10.1038/289555a0. [DOI] [PubMed] [Google Scholar]
  15. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  16. Laporte J., Grosclaude J., Wantyghem J., Bernard S., Rouzé P. Neutralisation en culture cellulaire du pouvoir infectieuz du virus de la fièvre aphteuse par des sérums provenant de porcs immunisés à l'aide d'une protéine virale purifiée. C R Acad Sci Hebd Seances Acad Sci D. 1973 Jun 18;276(25):3399–3401. [PubMed] [Google Scholar]
  17. Makoff A. J., Paynter C. A., Rowlands D. J., Boothroyd J. C. Comparison of the amino acid sequence of the major immunogen from three serotypes of foot and mouth disease virus. Nucleic Acids Res. 1982 Dec 20;10(24):8285–8295. doi: 10.1093/nar/10.24.8285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Meloen R. H., Briaire J., Woortmeyer R. J., van Zaane D. The main antigenic determinant detected by neutralizing monoclonal antibodies on the intact foot-and-mouth disease virus particle is absent from isolated VPI. J Gen Virol. 1983 May;64(Pt 5):1193–1198. doi: 10.1099/0022-1317-64-5-1193. [DOI] [PubMed] [Google Scholar]
  19. Palmenberg A. C., Kirby E. M., Janda M. R., Drake N. L., Duke G. M., Potratz K. F., Collett M. S. The nucleotide and deduced amino acid sequences of the encephalomyocarditis viral polyprotein coding region. Nucleic Acids Res. 1984 Mar 26;12(6):2969–2985. doi: 10.1093/nar/12.6.2969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pfaff E., Mussgay M., Böhm H. O., Schulz G. E., Schaller H. Antibodies against a preselected peptide recognize and neutralize foot and mouth disease virus. EMBO J. 1982;1(7):869–874. doi: 10.1002/j.1460-2075.1982.tb01262.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pfaff E., Thiel H. J., Böhm H. O., Leban J. Peptide vaccine--a new approach to a safer foot-and-mouth disease virus vaccine. Arzneimittelforschung. 1987 Jan;37(1):82–86. [PubMed] [Google Scholar]
  22. Rossmann M. G., Arnold E., Erickson J. W., Frankenberger E. A., Griffith J. P., Hecht H. J., Johnson J. E., Kamer G., Luo M., Mosser A. G. Structure of a human common cold virus and functional relationship to other picornaviruses. Nature. 1985 Sep 12;317(6033):145–153. doi: 10.1038/317145a0. [DOI] [PubMed] [Google Scholar]
  23. Rowlands D. J., Clarke B. E., Carroll A. R., Brown F., Nicholson B. H., Bittle J. L., Houghten R. A., Lerner R. A. Chemical basis of antigenic variation in foot-and-mouth disease virus. Nature. 1983 Dec 15;306(5944):694–697. doi: 10.1038/306694a0. [DOI] [PubMed] [Google Scholar]
  24. Ruoslahti E., Pierschbacher M. D. Arg-Gly-Asp: a versatile cell recognition signal. Cell. 1986 Feb 28;44(4):517–518. doi: 10.1016/0092-8674(86)90259-x. [DOI] [PubMed] [Google Scholar]
  25. Sangar D. V., Black D. N., Rowlands D. J., Brown F. Biochemical mapping of the foot-and-mouth disease virus genome. J Gen Virol. 1977 May;35(2):281–297. doi: 10.1099/0022-1317-35-2-281. [DOI] [PubMed] [Google Scholar]
  26. Sangar D. V. The replication of picornaviruses. J Gen Virol. 1979 Oct;45(1):1–13. doi: 10.1099/0022-1317-45-1-1. [DOI] [PubMed] [Google Scholar]
  27. Sherry B., Mosser A. G., Colonno R. J., Rueckert R. R. Use of monoclonal antibodies to identify four neutralization immunogens on a common cold picornavirus, human rhinovirus 14. J Virol. 1986 Jan;57(1):246–257. doi: 10.1128/jvi.57.1.246-257.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Stave J. W., Card J. L., Morgan D. O. Analysis of foot-and-mouth disease virus type O1 Brugge neutralization epitopes using monoclonal antibodies. J Gen Virol. 1986 Oct;67(Pt 10):2083–2092. doi: 10.1099/0022-1317-67-10-2083. [DOI] [PubMed] [Google Scholar]
  29. Strohmaier K., Franze R., Adam K. H. Location and characterization of the antigenic portion of the FMDV immunizing protein. J Gen Virol. 1982 Apr;59(Pt 2):295–306. doi: 10.1099/0022-1317-59-2-295. [DOI] [PubMed] [Google Scholar]
  30. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Xie Q. C., McCahon D., Crowther J. R., Belsham G. J., McCullough K. C. Neutralization of foot-and-mouth disease virus can be mediated through any of at least three separate antigenic sites. J Gen Virol. 1987 Jun;68(Pt 6):1637–1647. doi: 10.1099/0022-1317-68-6-1637. [DOI] [PubMed] [Google Scholar]
  32. Zimmern D., Kaesberg P. 3'-terminal nucleotide sequence of encephalomyocarditis virus RNA determined by reverse transcriptase and chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1978 Sep;75(9):4257–4261. doi: 10.1073/pnas.75.9.4257. [DOI] [PMC free article] [PubMed] [Google Scholar]

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