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. 1990 Nov;64(11):5519–5528. doi: 10.1128/jvi.64.11.5519-5528.1990

Unique amino acid substitutions in the capsid proteins of foot-and-mouth disease virus from a persistent infection in cell culture.

J Díez 1, M Dávila 1, C Escarmís 1, M G Mateu 1, J Dominguez 1, J J Pérez 1, E Giralt 1, J A Melero 1, E Domingo 1
PMCID: PMC248604  PMID: 2170684

Abstract

Maintenance of a persistent foot-and-mouth disease virus (FMDV) infection in BHK-21 cells involves a coevolution of cells and virus (J. C. de la Torre, E. Martínez-Salas, J. Díez, A. Villaverde, F. Gebauer, E. Rocha, M. Dávila, and E. Domingo, J. Virol. 62:2050-2058, 1988). The resident FMDV undergoes a number of phenotypic changes, including a gradual decrease in virion stability. Here we report the nucleotide sequence of the P1 genomic segment of the virus rescued after 100 passages of the carrier cells (R100). Only 5 of 15 mutations in P1 of R100 were silent. Nine amino acid substitutions were fixed on the viral capsid during persistence, and three of the variant amino acids are not represented in the corresponding position of any picornavirus sequenced to date. Cysteine at position 7 of VP3, that provides disulfide bridges at the FMDV fivefold axis, was substituted by valine, as determined by RNA, cDNA, and protein sequencing. The modified virus shows high buoyant density in cesium chloride and depicts the same sensitivity to photoinactivation by intercalating dyes as the parental FMDV C-S8c1. Amino acid substitutions fixed in VP1 resulted in altered antigenicity, as revealed by reactivity with monoclonal antibodies. In addition to defining at the molecular level the alterations the FMDV capsid underwent during persistence, the results show that positions which are highly invariant in an RNA genome may change when viral replication occurs in a modified environment.

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Selected References

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

  1. 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]
  2. 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]
  3. Burrows R. Studies on the carrier state of cattle exposed to foot-and-mouth disease virus. J Hyg (Lond) 1966 Mar;64(1):81–90. doi: 10.1017/s0022172400040365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chow M., Newman J. F., Filman D., Hogle J. M., Rowlands D. J., Brown F. Myristylation of picornavirus capsid protein VP4 and its structural significance. Nature. 1987 Jun 11;327(6122):482–486. doi: 10.1038/327482a0. [DOI] [PubMed] [Google Scholar]
  5. DeBorde D. C., Naeve C. W., Herlocher M. L., Maassab H. F. Resolution of a common RNA sequencing ambiguity by terminal deoxynucleotidyl transferase. Anal Biochem. 1986 Sep;157(2):275–282. doi: 10.1016/0003-2697(86)90626-3. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Diez J., Mateu M. G., Domingo E. Selection of antigenic variants of foot-and-mouth disease virus in the absence of antibodies, as revealed by an in situ assay. J Gen Virol. 1989 Dec;70(Pt 12):3281–3289. doi: 10.1099/0022-1317-70-12-3281. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Domingo E. RNA virus evolution and the control of viral disease. Prog Drug Res. 1989;33:93–133. doi: 10.1007/978-3-0348-9146-2_5. [DOI] [PubMed] [Google Scholar]
  10. Dunn S. D. Effects of the modification of transfer buffer composition and the renaturation of proteins in gels on the recognition of proteins on Western blots by monoclonal antibodies. Anal Biochem. 1986 Aug 15;157(1):144–153. doi: 10.1016/0003-2697(86)90207-1. [DOI] [PubMed] [Google Scholar]
  11. Feng D. F., Johnson M. S., Doolittle R. F. Aligning amino acid sequences: comparison of commonly used methods. J Mol Evol. 1984;21(2):112–125. doi: 10.1007/BF02100085. [DOI] [PubMed] [Google Scholar]
  12. Forss S., Strebel K., Beck E., Schaller H. Nucleotide sequence and genome organization of foot-and-mouth disease virus. Nucleic Acids Res. 1984 Aug 24;12(16):6587–6601. doi: 10.1093/nar/12.16.6587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Hampar B., Keehn M. A. Cumulative changes in the antigenic properties of herpes simplex virus from persistently infected cell cultures. J Immunol. 1967 Sep;99(3):554–557. [PubMed] [Google Scholar]
  15. Hedger R. S., Condy J. B. Transmission of foot-and-mouth disease from African buffalo virus carriers to bovines. Vet Rec. 1985 Aug 31;117(9):205–205. doi: 10.1136/vr.117.9.205-a. [DOI] [PubMed] [Google Scholar]
  16. Hedger R. S. The isolation and characterization of foot-and-mouth disease virus from clinically normal herds of cattle in Botswana. J Hyg (Lond) 1968 Mar;66(1):27–36. doi: 10.1017/s0022172400040912. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hewick R. M., Hunkapiller M. W., Hood L. E., Dreyer W. J. A gas-liquid solid phase peptide and protein sequenator. J Biol Chem. 1981 Aug 10;256(15):7990–7997. [PubMed] [Google Scholar]
  18. 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]
  19. Kraft R., Tardiff J., Krauter K. S., Leinwand L. A. Using mini-prep plasmid DNA for sequencing double stranded templates with Sequenase. Biotechniques. 1988 Jun;6(6):544-6, 549. [PubMed] [Google Scholar]
  20. 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]
  21. Lapeyre B., Amalric F. A powerful method for the preparation of cDNA libraries: isolation of cDNA encoding a 100-kDal nucleolar protein. Gene. 1985;37(1-3):215–220. doi: 10.1016/0378-1119(85)90275-6. [DOI] [PubMed] [Google Scholar]
  22. Luo M., Rossmann M. G., Palmenberg A. C. Prediction of three-dimensional models for foot-and-mouth disease virus and hepatitis A virus. Virology. 1988 Oct;166(2):503–514. doi: 10.1016/0042-6822(88)90521-1. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. 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]
  25. Mateu M. G., Martínez M. A., Capucci L., Andreu D., Giralt E., Sobrino F., Brocchi E., Domingo E. A single amino acid substitution affects multiple overlapping epitopes in the major antigenic site of foot-and-mouth disease virus of serotype C. J Gen Virol. 1990 Mar;71(Pt 3):629–637. doi: 10.1099/0022-1317-71-3-629. [DOI] [PubMed] [Google Scholar]
  26. Mateu M. G., Martínez M. A., Rocha E., Andreu D., Parejo J., Giralt E., Sobrino F., Domingo E. Implications of a quasispecies genome structure: effect of frequent, naturally occurring amino acid substitutions on the antigenicity of foot-and-mouth disease virus. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5883–5887. doi: 10.1073/pnas.86.15.5883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. 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]
  28. 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]
  29. Richardson J. S. The anatomy and taxonomy of protein structure. Adv Protein Chem. 1981;34:167–339. doi: 10.1016/s0065-3233(08)60520-3. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Sobrino F., Martinez M. A., Carrillo C., Beck E. Antigenic variation of foot-and-mouth disease virus of serotype C during propagation in the field is mainly restricted to only one structural protein (VP1). Virus Res. 1989 Dec;14(4):273–280. doi: 10.1016/0168-1702(89)90021-x. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Staden R. A new computer method for the storage and manipulation of DNA gel reading data. Nucleic Acids Res. 1980 Aug 25;8(16):3673–3694. doi: 10.1093/nar/8.16.3673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. 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]
  35. 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]
  36. Sutmoller P., Gaggero A. Foot-and mouth diseases carriers. Vet Rec. 1965 Aug 14;77(33):968–969. doi: 10.1136/vr.77.33.968. [DOI] [PubMed] [Google Scholar]
  37. Sutmoller P., McVicar J. W., Cottral G. E. The epizootiological importance of foot-and-mouth disease carriers. I. Experimentally produced foot-and-mouth disease carriers in susceptible and immune cattle. Arch Gesamte Virusforsch. 1968;23(3):227–235. doi: 10.1007/BF01241895. [DOI] [PubMed] [Google Scholar]
  38. Tabor S., Richardson C. C. DNA sequence analysis with a modified bacteriophage T7 DNA polymerase. Proc Natl Acad Sci U S A. 1987 Jul;84(14):4767–4771. doi: 10.1073/pnas.84.14.4767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Thomas A. A., Woortmeijer R. J., Puijk W., Barteling S. J. Antigenic sites on foot-and-mouth disease virus type A10. J Virol. 1988 Aug;62(8):2782–2789. doi: 10.1128/jvi.62.8.2782-2789.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Vandekerckhove J., Bauw G., Puype M., Van Damme J., Van Montagu M. Protein-blotting on Polybrene-coated glass-fiber sheets. A basis for acid hydrolysis and gas-phase sequencing of picomole quantities of protein previously separated on sodium dodecyl sulfate/polyacrylamide gel. Eur J Biochem. 1985 Oct 1;152(1):9–19. doi: 10.1111/j.1432-1033.1985.tb09157.x. [DOI] [PubMed] [Google Scholar]
  41. Villanueva N., Dávila M., Ortín J., Domingo E. Molecular cloning of cDNA from foot-and-mouth disease virus C1-Santa Pau (C-S8). Sequence of protein-VP1-coding segment. Gene. 1983 Aug;23(2):185–194. doi: 10.1016/0378-1119(83)90050-1. [DOI] [PubMed] [Google Scholar]
  42. Villaverde A., Martínez-Salas E., Domingo E. 3D gene of foot-and-mouth disease virus. Conservation by convergence of average sequences. J Mol Biol. 1988 Dec 5;204(3):771–776. doi: 10.1016/0022-2836(88)90367-1. [DOI] [PubMed] [Google Scholar]
  43. Weddell G. N., Yansura D. G., Dowbenko D. J., Hoatlin M. E., Grubman M. J., Moore D. M., Kleid D. G. Sequence variation in the gene for the immunogenic capsid protein VP1 of foot-and-mouth disease virus type A. Proc Natl Acad Sci U S A. 1985 May;82(9):2618–2622. doi: 10.1073/pnas.82.9.2618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. 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]
  45. de la Torre J. C., Alarcón B., Martínez-Salas E., Carrasco L., Domingo E. Ribavirin cures cells of a persistent infection with foot-and-mouth disease virus in vitro. J Virol. 1987 Jan;61(1):233–235. doi: 10.1128/jvi.61.1.233-235.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. de la Torre J. C., Dávila M., Sobrino F., Ortín J., Domingo E. Establishment of cell lines persistently infected with foot-and-mouth disease virus. Virology. 1985 Aug;145(1):24–35. doi: 10.1016/0042-6822(85)90198-9. [DOI] [PubMed] [Google Scholar]
  47. de la Torre J. C., 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. doi: 10.1128/jvi.62.6.2050-2058.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. de la Torre J. C., Martínez-Salas E., Díez J., Domingo E. Extensive cell heterogeneity during persistent infection with foot-and-mouth disease virus. J Virol. 1989 Jan;63(1):59–63. doi: 10.1128/jvi.63.1.59-63.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. de la Torre J. C., Ortín J., Domingo E., Delamarter J., Allet B., Davies J., Bertrand K. P., Wray L. V., Jr, Reznikoff W. S. Plasmid vectors based on Tn10 DNA: gene expression regulated by tetracycline. Plasmid. 1984 Sep;12(2):103–110. doi: 10.1016/0147-619x(84)90056-8. [DOI] [PubMed] [Google Scholar]
  50. de la Torre J. C., de la Luna S., Diez J., Domingo E. Resistance to foot-and-mouth disease virus mediated by trans-acting cellular products. J Virol. 1989 May;63(5):2385–2387. doi: 10.1128/jvi.63.5.2385-2387.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]

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