Logo of jvirolPermissionsJournals.ASM.orgJournalJV ArticleJournal InfoAuthorsReviewers
J Virol. 1989 May; 63(5): 2143–2151.
PMCID: PMC250631

Analysis of neutralizing antigenic sites on the surface of type A12 foot-and-mouth disease virus.


A series of seven neutralizing monoclonal antibodies (nMAbs) directed against type A12 foot-and-mouth disease virus was used to generate neutralization-resistant variants. Both plaque reduction neutralization and microneutralization assays showed that the variants were no longer neutralized by the nMAbs used to generate them, although some of the variants still reacted with the nMAbs at high antibody concentrations. Results of cross-neutralization studies by both plaque reduction neutralization and microneutralization assays suggested the presence of at least one immunodominant antigenic site on the surface of type A12 foot-and-mouth disease virus, along with evidence of a second antigenic site on the viral surface. Two of the variants had reduced virulence in tissue culture as evidenced by their inability to inhibit cellular protein synthesis and a marked reduction in virus-induced cellular morphological alterations. Nucleotide sequencing of the variant genomes placed three epitopes of the major antigenic site on VP1 and the fourth epitope on VP3 and VP1. The one epitope of the minor site appears to reside only on VP1.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.9M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Agol VI, Drozdov SG, Frolova MP, Grachev VP, Kolesnikova MS, Kozlov VG, Ralph NM, Romanova LI, Tolskaya EA, Viktorova EG. Neurovirulence of the intertypic poliovirus recombinant v3/a1-25: characterization of strains isolated from the spinal cord of diseased monkeys and evaluation of the contribution of the 3' half of the genome. J Gen Virol. 1985 Feb;66(Pt 2):309–316. [PubMed]
  • Agol VI, Drozdov SG, Grachev VP, Kolesnikova MS, Kozlov VG, Ralph NM, Romanova LI, Tolskaya EA, Tyufanov AV, Viktorova EG. Recombinants between attenuated and virulent strains of poliovirus type 1: derivation and characterization of recombinants with centrally located crossover points. Virology. 1985 Jun;143(2):467–477. [PubMed]
  • Bachrach HL, Moore DM, McKercher PD, 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]
  • Bachrach HL, Morgan DO, McKercher PD, Moore DM, Robertson BH. Foot-and-mouth disease virus: immunogenicity and structure of fragments derived from capsid protein VP and of virus containing cleaved VP. Vet Microbiol. 1982 May;7(2):85–96. [PubMed]
  • Bachrach HL, Morgan DO, Moore DM. Foot-and-mouth disease virus immunogenic capsid protein VPT: N-terminal sequences and immunogenic peptides obtained by CNBr and tryptic cleavages. Intervirology. 1979;12(2):65–72. [PubMed]
  • Baxt B. Effect of lysosomotropic compounds on early events in foot-and-mouth disease virus replication. Virus Res. 1987 May;7(3):257–271. [PubMed]
  • Baxt B, Bachrach HL. Early interactions of foot-and-mouth disease virus with cultured cells. Virology. 1980 Jul 15;104(1):42–55. [PubMed]
  • Baxt B, Bachrach HL. The adsorption and degradation of foot-and-mouth disease virus by isolated BHK-21 cell plasma membranes. Virology. 1982 Jan 30;116(2):391–405. [PubMed]
  • Baxt B, Morgan DO, Robertson BH, Timpone CA. 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. [PMC free article] [PubMed]
  • Bittle JL, Houghten RA, Alexander H, Shinnick TM, Sutcliffe JG, Lerner RA, Rowlands DJ, 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. [PubMed]
  • Blaas D, Kuechler E, Vriend G, Arnold E, Luo M, Rossmann MG. Comparison of the three-dimensional structure of two human rhinoviruses (HRV2 and HRV14). Proteins. 1987;2(4):263–272. [PubMed]
  • 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. [PMC free article] [PubMed]
  • Cann AJ, Stanway G, Hughes PJ, Minor PD, Evans DM, Schild GC, Almond JW. Reversion to neurovirulence of the live-attenuated Sabin type 3 oral poliovirus vaccine. Nucleic Acids Res. 1984 Oct 25;12(20):7787–7792. [PMC free article] [PubMed]
  • Chow M, Newman JF, Filman D, Hogle JM, Rowlands DJ, Brown F. Myristylation of picornavirus capsid protein VP4 and its structural significance. Nature. 1987 Jun 11;327(6122):482–486. [PubMed]
  • de la Torre JC, Martínez-Salas E, Diez J, Villaverde A, Gebauer F, Rocha E, Dávila M, Domingo E. Coevolution of cells and viruses in a persistent infection of foot-and-mouth disease virus in cell culture. J Virol. 1988 Jun;62(6):2050–2058. [PMC free article] [PubMed]
  • Diamond DC, Jameson BA, Bonin J, Kohara M, Abe S, Itoh H, Komatsu T, Arita M, Kuge S, Nomoto A, et al. Antigenic variation and resistance to neutralization in poliovirus type 1. Science. 1985 Sep 13;229(4718):1090–1093. [PubMed]
  • 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. [PubMed]
  • Evans DM, Dunn G, Minor PD, Schild GC, Cann AJ, Stanway G, Almond JW, Currey K, Maizel JV., Jr Increased neurovirulence associated with a single nucleotide change in a noncoding region of the Sabin type 3 poliovaccine genome. Nature. 1985 Apr 11;314(6011):548–550. [PubMed]
  • Evans DM, Minor PD, Schild GS, Almond JW. Critical role of an eight-amino acid sequence of VP1 in neutralization of poliovirus type 3. Nature. 1983 Aug 4;304(5925):459–462. [PubMed]
  • Fox G, Stuart D, Acharya KR, Fry E, Rowlands D, Brown F. Crystallization and preliminary X-ray diffraction analysis of foot-and-mouth disease virus. J Mol Biol. 1987 Aug 5;196(3):591–597. [PubMed]
  • Gebauer F, de la Torre JC, Gomes I, Mateu MG, Barahona H, Tiraboschi B, Bergmann I, de Mello PA, Domingo E. Rapid selection of genetic and antigenic variants of foot-and-mouth disease virus during persistence in cattle. J Virol. 1988 Jun;62(6):2041–2049. [PMC free article] [PubMed]
  • Grubman MJ, Baxt B. Translation of foot-and-mouth disease virion RNA and processing of the primary cleavage products in a rabbit reticulocyte lysate. Virology. 1982 Jan 15;116(1):19–30. [PubMed]
  • Grubman MJ, Morgan DO. Antigenic comparison of foot-and-mouth disease virus serotypes with monoclonal antibodies. Virus Res. 1986 Oct;6(1):33–43. [PubMed]
  • Grubman MJ, Morgan DO, Kendall J, Baxt B. Capsid intermediates assembled in a foot-and-mouth disease virus genome RNA-programmed cell-free translation system and in infected cells. J Virol. 1985 Oct;56(1):120–126. [PMC free article] [PubMed]
  • Hogle JM, Chow M, Filman DJ. Three-dimensional structure of poliovirus at 2.9 A resolution. Science. 1985 Sep 27;229(4720):1358–1365. [PubMed]
  • Kleid DG, Yansura D, Small B, Dowbenko D, Moore DM, Grubman MJ, McKercher PD, Morgan DO, Robertson BH, Bachrach HL. Cloned viral protein vaccine for foot-and-mouth disease: responses in cattle and swine. Science. 1981 Dec 4;214(4525):1125–1129. [PubMed]
  • Lo KM, Jones SS, Hackett NR, Khorana HG. Specific amino acid substitutions in bacterioopsin: Replacement of a restriction fragment in the structural gene by synthetic DNA fragments containing altered codons. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2285–2289. [PMC free article] [PubMed]
  • Luo M, Rossmann MG, Palmenberg AC. Prediction of three-dimensional models for foot-and-mouth disease virus and hepatitis A virus. Virology. 1988 Oct;166(2):503–514. [PubMed]
  • Martinez MA, Carrillo C, Plana J, Mascarella R, Bergada J, Palma EL, Domingo E, Sobrino F. Genetic and immunogenic variations among closely related isolates of foot-and-mouth disease virus. Gene. 1988;62(1):75–84. [PubMed]
  • McCullough KC, Crowther JR, Carpenter WC, Brocchi E, Capucci L, De Simone F, Xie Q, McCahon D. Epitopes on foot-and-mouth disease virus particles. I. Topology. Virology. 1987 Apr;157(2):516–525. [PubMed]
  • Meloen RH, Barteling SJ. An epitope located at the C terminus of isolated VP1 of foot-and-mouth disease virus type O induces neutralizing activity but poor protection. J Gen Virol. 1986 Feb;67(Pt 2):289–294. [PubMed]
  • Meloen RH, Barteling SJ. Epitope mapping of the outer structural protein VP1 of three different serotypes of foot-and-mouth disease virus. Virology. 1986 Feb;149(1):55–63. [PubMed]
  • Meloen RH, Puyk WC, Meijer DJ, Lankhof H, Posthumus WP, Schaaper WM. Antigenicity and immunogenicity of synthetic peptides of foot-and-mouth disease virus. J Gen Virol. 1987 Feb;68(Pt 2):305–314. [PubMed]
  • Mills DR, Kramer FR. Structure-independent nucleotide sequence analysis. Proc Natl Acad Sci U S A. 1979 May;76(5):2232–2235. [PMC free article] [PubMed]
  • Minor PD, Evans DM, Ferguson M, Schild GC, Westrop G, Almond JW. Principal and subsidiary antigenic sites of VP1 involved in the neutralization of poliovirus type 3. J Gen Virol. 1985 May;66(Pt 5):1159–1165. [PubMed]
  • Minor PD, Schild GC, Bootman J, Evans DM, Ferguson M, Reeve P, Spitz M, Stanway G, Cann AJ, Hauptmann R, et al. Location and primary structure of a major antigenic site for poliovirus neutralization. Nature. 1983 Feb 24;301(5902):674–679. [PubMed]
  • Morrell DJ, Mellor EJ, Rowlands DJ, Brown F. Surface structure and RNA-protein interactions of foot-and-mouth disease virus. J Gen Virol. 1987 Jun;68(Pt 6):1649–1658. [PubMed]
  • Page GS, Mosser AG, Hogle JM, Filman DJ, Rueckert RR, Chow M. Three-dimensional structure of poliovirus serotype 1 neutralizing determinants. J Virol. 1988 May;62(5):1781–1794. [PMC free article] [PubMed]
  • Parisi JM, Costa Giomi P, Grigera P, Augé de Mello P, Bergmann IE, La Torre JL, Scodeller EA. Biochemical characterization of an aphthovirus type 0(1) strain campos attenuated for cattle by serial passages in chicken embryos. Virology. 1985 Nov;147(1):61–71. [PubMed]
  • Pfaff E, Thiel HJ, Beck E, Strohmaier K, Schaller H. Analysis of neutralizing epitopes on foot-and-mouth disease virus. J Virol. 1988 Jun;62(6):2033–2040. [PMC free article] [PubMed]
  • Prabhakar BS, Srinivasappa J, Ray U. Selection of coxsackievirus B4 variants with monoclonal antibodies results in attenuation. J Gen Virol. 1987 Mar;68(Pt 3):865–869. [PubMed]
  • Robertson BH, Grubman MJ, Weddell GN, Moore DM, Welsh JD, Fischer T, Dowbenko DJ, Yansura DG, Small B, Kleid DG. Nucleotide and amino acid sequence coding for polypeptides of foot-and-mouth disease virus type A12. J Virol. 1985 Jun;54(3):651–660. [PMC free article] [PubMed]
  • Robertson BH, Moore DM, Grubman MJ, Kleid DG. Identification of an exposed region of the immunogenic capsid polypeptide VP1 on foot-and-mouth disease virus. J Virol. 1983 Apr;46(1):311–316. [PMC free article] [PubMed]
  • Robertson BH, Morgan DO, Moore DM. Location of neutralizing epitopes defined by monoclonal antibodies generated against the outer capsid polypeptide, VP1, of foot-and-mouth disease virus A12. Virus Res. 1984 Sep;1(6):489–500. [PubMed]
  • Rossmann MG, Arnold E, Erickson JW, Frankenberger EA, Griffith JP, Hecht HJ, Johnson JE, Kamer G, Luo M, Mosser AG, et al. Structure of a human common cold virus and functional relationship to other picornaviruses. Nature. 1985 Sep 12;317(6033):145–153. [PubMed]
  • Rowlands DJ, Clarke BE, Carroll AR, Brown F, Nicholson BH, Bittle JL, Houghten RA, Lerner RA. Chemical basis of antigenic variation in foot-and-mouth disease virus. Nature. 1983 Dec 15;306(5944):694–697. [PubMed]
  • Sagedahl A, Giraudo AT, De Mello PA, Bergmann IE, La Torre JL, Scodeller EA. Biochemical characterization of an aphthovirus type C3 strain Resende attenuated for cattle by serial passages in chicken embryos. Virology. 1987 Apr;157(2):366–374. [PubMed]
  • Sherry B, Mosser AG, Colonno RJ, Rueckert RR. 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. [PMC free article] [PubMed]
  • Sherry B, Rueckert R. Evidence for at least two dominant neutralization antigens on human rhinovirus 14. J Virol. 1985 Jan;53(1):137–143. [PMC free article] [PubMed]
  • Sobrino F, Dávila M, Ortín J, Domingo E. Multiple genetic variants arise in the course of replication of foot-and-mouth disease virus in cell culture. Virology. 1983 Jul 30;128(2):310–318. [PubMed]
  • Sobrino F, Palma EL, Beck E, Dávila M, de la Torre JC, Negro P, Villanueva N, Ortín J, Domingo E. Fixation of mutations in the viral genome during an outbreak of foot-and-mouth disease: heterogeneity and rate variations. Gene. 1986;50(1-3):149–159. [PubMed]
  • Stapleton JT, Lemon SM. Neutralization escape mutants define a dominant immunogenic neutralization site on hepatitis A virus. J Virol. 1987 Feb;61(2):491–498. [PMC free article] [PubMed]
  • Stave JW, Card JL, Morgan DO. 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. [PubMed]
  • Stave JW, Card JL, Morgan DO, Vakharia VN. Neutralization sites of type O1 foot-and-mouth disease virus defined by monoclonal antibodies and neutralization-escape virus variants. Virology. 1988 Jan;162(1):21–29. [PubMed]
  • Strohmaier K, Franze R, Adam KH. Location and characterization of the antigenic portion of the FMDV immunizing protein. J Gen Virol. 1982 Apr;59(Pt 2):295–306. [PubMed]
  • Thomas AA, Woortmeijer RJ, Puijk W, Barteling SJ. Antigenic sites on foot-and-mouth disease virus type A10. J Virol. 1988 Aug;62(8):2782–2789. [PMC free article] [PubMed]
  • Trautman R, Harris WF. Modeling and computer stimulation approach to the mechanism of foot-and-mouth disease virus neutralization assays. Scand J Immunol. 1977;6(8):831–841. [PubMed]
  • Wiegers K, Uhlig H, Dernick R. Evidence for a complex structure of neutralization antigenic site I of poliovirus type 1 Mahoney. J Virol. 1988 May;62(5):1845–1848. [PMC free article] [PubMed]
  • Xie QC, McCahon D, Crowther JR, Belsham GJ, McCullough KC. 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. [PubMed]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...