Abstract
We provide evidence that the quasispecies nature (extreme genetic heterogeneity) of foot-and-mouth disease virus is relevant to the virus evading an immune response. A monoclonal antibody neutralizing the viral infectivity (clone SD6) recognizes an epitope located around a highly conserved sequence (amino acid sequence Arg-Gly-Asp-Leu-Ala at positions 141-145) in the capsid protein VP1 of foot-and-mouth disease virus of serotype C1. The amino acid substitutions Ala-138----Thr and Leu-147----Ile (or ----Val) reduced 100-fold the binding titer of monoclonal antibody SD6 to virions or to VP1. The effect of those substitutions was quantitatively reproduced with synthetic peptides representing the relevant sequences. This provides evidence that the two chemically conservative amino acids replacements--and not other substitutions present in the virus quasispecies--are responsible for the modified interaction with neutralizing monoclonal antibody SD6. The three substitutions were fixed in the viral capsid during one occurrence of foot-and-mouth disease and, furthermore, they are of a type found frequently among independent foot-and-mouth disease virus isolates. The results implicate the extreme heterogeneity of foot-and-mouth disease virus as an important element of viral pathogenesis.
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Selected References
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- Acharya R., Fry E., Stuart D., Fox G., Rowlands D., Brown F. The three-dimensional structure of foot-and-mouth disease virus at 2.9 A resolution. Nature. 1989 Feb 23;337(6209):709–716. doi: 10.1038/337709a0. [DOI] [PubMed] [Google Scholar]
- Bachrach H. L. Foot-and-mouth disease. Annu Rev Microbiol. 1968;22:201–244. doi: 10.1146/annurev.mi.22.100168.001221. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- 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]
- Domingo E., Dávila M., Ortín J. Nucleotide sequence heterogeneity of the RNA from a natural population of foot-and-mouth-disease virus. Gene. 1980 Nov;11(3-4):333–346. doi: 10.1016/0378-1119(80)90073-6. [DOI] [PubMed] [Google Scholar]
- Domingo E., Sabo D., Taniguchi T., Weissmann C. Nucleotide sequence heterogeneity of an RNA phage population. Cell. 1978 Apr;13(4):735–744. doi: 10.1016/0092-8674(78)90223-4. [DOI] [PubMed] [Google Scholar]
- Dopazo J., Sobrino F., Palma E. L., Domingo E., Moya A. Gene encoding capsid protein VP1 of foot-and-mouth disease virus: a quasispecies model of molecular evolution. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6811–6815. doi: 10.1073/pnas.85.18.6811. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eigen M. Selforganization of matter and the evolution of biological macromolecules. Naturwissenschaften. 1971 Oct;58(10):465–523. doi: 10.1007/BF00623322. [DOI] [PubMed] [Google Scholar]
- Fox G., Parry N. R., Barnett P. V., McGinn B., Rowlands D. J., Brown F. The cell attachment site on foot-and-mouth disease virus includes the amino acid sequence RGD (arginine-glycine-aspartic acid). J Gen Virol. 1989 Mar;70(Pt 3):625–637. doi: 10.1099/0022-1317-70-3-625. [DOI] [PubMed] [Google Scholar]
- Francis M. J., Hastings G. Z., Syred A. D., McGinn B., Brown F., Rowlands D. J. Non-responsiveness to a foot-and-mouth disease virus peptide overcome by addition of foreign helper T-cell determinants. Nature. 1987 Nov 12;330(6144):168–170. doi: 10.1038/330168a0. [DOI] [PubMed] [Google Scholar]
- Gebauer F., de la Torre J. C., Gomes I., Mateu M. G., Barahona H., Tiraboschi B., Bergmann I., de Mello P. A., 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. doi: 10.1128/jvi.62.6.2041-2049.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Geysen H. M., Barteling S. J., Meloen R. H. Small peptides induce antibodies with a sequence and structural requirement for binding antigen comparable to antibodies raised against the native protein. Proc Natl Acad Sci U S A. 1985 Jan;82(1):178–182. doi: 10.1073/pnas.82.1.178. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Holland J., Spindler K., Horodyski F., Grabau E., Nichol S., VandePol S. Rapid evolution of RNA genomes. Science. 1982 Mar 26;215(4540):1577–1585. doi: 10.1126/science.7041255. [DOI] [PubMed] [Google Scholar]
- Kitagawa T., Aikawa T. Enzyme coupled immunoassay of insulin using a novel coupling reagent. J Biochem. 1976 Jan;79(1):233–236. doi: 10.1093/oxfordjournals.jbchem.a131053. [DOI] [PubMed] [Google Scholar]
- Levitt M. Conformational preferences of amino acids in globular proteins. Biochemistry. 1978 Oct 3;17(20):4277–4285. doi: 10.1021/bi00613a026. [DOI] [PubMed] [Google Scholar]
- Mariuzza R. A., Phillips S. E., Poljak R. J. The structural basis of antigen-antibody recognition. Annu Rev Biophys Biophys Chem. 1987;16:139–159. doi: 10.1146/annurev.bb.16.060187.001035. [DOI] [PubMed] [Google Scholar]
- Martinez M. A., Carrillo C., Plana J., Mascarella R., Bergada J., Palma E. L., Domingo E., Sobrino F. Genetic and immunogenic variations among closely related isolates of foot-and-mouth disease virus. Gene. 1988;62(1):75–84. doi: 10.1016/0378-1119(88)90581-1. [DOI] [PubMed] [Google Scholar]
- Mateu M. G., Da Silva J. L., Rocha E., De Brum D. L., Alonso A., Enjuanes L., Domingo E., Barahona H. Extensive antigenic heterogeneity of foot-and-mouth disease virus of serotype C. Virology. 1988 Nov;167(1):113–124. doi: 10.1016/0042-6822(88)90060-8. [DOI] [PubMed] [Google Scholar]
- Mateu M. G., Rocha E., Vicente O., Vayreda F., Navalpotro C., Andreu D., Pedroso E., Giralt E., Enjuanes L., Domingo E. Reactivity with monoclonal antibodies of viruses from an episode of foot-and-mouth disease. Virus Res. 1987 Sep;8(3):261–274. doi: 10.1016/0168-1702(87)90020-7. [DOI] [PubMed] [Google Scholar]
- 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]
- Pfaff E., Thiel H. J., Beck E., Strohmaier K., Schaller H. Analysis of neutralizing epitopes on foot-and-mouth disease virus. J Virol. 1988 Jun;62(6):2033–2040. doi: 10.1128/jvi.62.6.2033-2040.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Piccone M. E., Kaplan G., Giavedoni L., Domingo E., Palma E. L. VP1 of serotype C foot-and-mouth disease viruses: long-term conservation of sequences. J Virol. 1988 Apr;62(4):1469–1473. doi: 10.1128/jvi.62.4.1469-1473.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Siliciano R. F., Lawton T., Knall C., Karr R. W., Berman P., Gregory T., Reinherz E. L. Analysis of host-virus interactions in AIDS with anti-gp120 T cell clones: effect of HIV sequence variation and a mechanism for CD4+ cell depletion. Cell. 1988 Aug 12;54(4):561–575. doi: 10.1016/0092-8674(88)90078-5. [DOI] [PubMed] [Google Scholar]
- 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. doi: 10.1016/0042-6822(83)90258-1. [DOI] [PubMed] [Google Scholar]
- Sobrino F., Palma E. L., Beck E., Dávila M., de la Torre J. C., 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. doi: 10.1016/0378-1119(86)90320-3. [DOI] [PubMed] [Google Scholar]
- Stave J. W., Card J. L., Morgan D. O., Vakharia V. N. 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. doi: 10.1016/0042-6822(88)90390-x. [DOI] [PubMed] [Google Scholar]
- Steinhauer D. A., Holland J. J. Rapid evolution of RNA viruses. Annu Rev Microbiol. 1987;41:409–433. doi: 10.1146/annurev.mi.41.100187.002205. [DOI] [PubMed] [Google Scholar]
- 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]