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J Virol. Jul 1997; 71(7): 5115–5123.
PMCID: PMC191746

Tissue culture adaptation of foot-and-mouth disease virus selects viruses that bind to heparin and are attenuated in cattle.

Abstract

Isolates of foot-and-mouth disease virus (FMDV) exist as complex mixtures of variants. Two different serotype O1 Campos preparations that we examined contained two variants with distinct plaque morphologies on BHK cells: a small, clear-plaque virus that replicates in BHK and CHO cells, and a large, turbid-plaque virus that only grows in BHK cells. cDNAs encoding the capsids of these two variants were inserted into a genome-length FMDV type A12 infectious cDNA and used to produce chimeric viruses that exhibited the phenotype of the original variants. Analyses of these viruses, and hybrids created by exchanging portions of the capsid gene, identified codon 56 in VP3 (3056) as the critical determinant of both cell tropism and plaque phenotype. Specifically, the CHO growth/clear-plaque phenotype is dependent on the presence of the highly charged Arg residue at 3056, and viruses with this phenotype and genotype were selected during propagation in tissue culture. The genetically engineered Arg 3056 virus was highly attenuated in bovines, but viruses recovered from animals inoculated with high doses of this virus had lost the ability to grow in CHO cells and contained either an uncharged residue at 3056 or a negatively charged Glu substituted for a Lys at a spatially and antigenically related position on VP2 (2134). Comparison of these animal-derived viruses to other natural and engineered viruses demonstrated that positively charged residues are required at both 2134 and 3056 for binding to heparin. Taken together, these results indicate that in vitro cultivation of FMDV type O selects viruses that bind to heparin and that viruses with the heparin-binding phenotype are attenuated in the natural host.

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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. [PubMed]
  • Alonso A, Darsie GC, Teixeira AC, Reis JL, Mesquita JA. Application of monoclonal antibodies to quality control of foot-and-mouth disease vaccines. Vaccine. 1994 Jun;12(8):682–686. [PubMed]
  • Baxt B, Becker Y. The effect of peptides containing the arginine-glycine-aspartic acid sequence on the adsorption of foot-and-mouth disease virus to tissue culture cells. Virus Genes. 1990 Jun;4(1):73–83. [PubMed]
  • Baxt B, Mason PW. Foot-and-mouth disease virus undergoes restricted replication in macrophage cell cultures following Fc receptor-mediated adsorption. Virology. 1995 Mar 10;207(2):503–509. [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]
  • Bergelson JM, Shepley MP, Chan BM, Hemler ME, Finberg RW. Identification of the integrin VLA-2 as a receptor for echovirus 1. Science. 1992 Mar 27;255(5052):1718–1720. [PubMed]
  • Berinstein A, Roivainen M, Hovi T, Mason PW, Baxt B. Antibodies to the vitronectin receptor (integrin alpha V beta 3) inhibit binding and infection of foot-and-mouth disease virus to cultured cells. J Virol. 1995 Apr;69(4):2664–2666. [PMC free article] [PubMed]
  • Bolwell C, Brown AL, Barnett PV, Campbell RO, Clarke BE, Parry NR, Ouldridge EJ, Brown F, Rowlands DJ. Host cell selection of antigenic variants of foot-and-mouth disease virus. J Gen Virol. 1989 Jan;70(Pt 1):45–57. [PubMed]
  • Chang KH, Auvinen P, Hyypiä T, Stanway G. The nucleotide sequence of coxsackievirus A9; implications for receptor binding and enterovirus classification. J Gen Virol. 1989 Dec;70(Pt 12):3269–3280. [PubMed]
  • 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. [PMC free article] [PubMed]
  • Fox G, Parry NR, Barnett PV, McGinn B, Rowlands DJ, 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. [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]
  • Hughes PJ, Horsnell C, Hyypiä T, Stanway G. The coxsackievirus A9 RGD motif is not essential for virus viability. J Virol. 1995 Dec;69(12):8035–8040. [PMC free article] [PubMed]
  • Jackson T, Ellard FM, Ghazaleh RA, Brookes SM, Blakemore WE, Corteyn AH, Stuart DI, Newman JW, King AM. Efficient infection of cells in culture by type O foot-and-mouth disease virus requires binding to cell surface heparan sulfate. J Virol. 1996 Aug;70(8):5282–5287. [PMC free article] [PubMed]
  • Jensen MJ, Moore DM. Phenotypic and functional characterization of mouse attenuated and virulent variants of foot-and-mouth disease virus type O1 Campos. Virology. 1993 Apr;193(2):604–613. [PubMed]
  • Kitson JD, McCahon D, Belsham GJ. Sequence analysis of monoclonal antibody resistant mutants of type O foot and mouth disease virus: evidence for the involvement of the three surface exposed capsid proteins in four antigenic sites. Virology. 1990 Nov;179(1):26–34. [PubMed]
  • Lea S, Abu-Ghazaleh R, Blakemore W, Curry S, Fry E, Jackson T, King A, Logan D, Newman J, Stuart D. Structural comparison of two strains of foot-and-mouth disease virus subtype O1 and a laboratory antigenic variant, G67. Structure. 1995 Jun 15;3(6):571–580. [PubMed]
  • Lea S, Hernández J, Blakemore W, Brocchi E, Curry S, Domingo E, Fry E, Abu-Ghazaleh R, King A, Newman J, et al. The structure and antigenicity of a type C foot-and-mouth disease virus. Structure. 1994 Feb 15;2(2):123–139. [PubMed]
  • Logan D, Abu-Ghazaleh R, Blakemore W, Curry S, Jackson T, King A, Lea S, Lewis R, Newman J, Parry N, et al. Structure of a major immunogenic site on foot-and-mouth disease virus. Nature. 1993 Apr 8;362(6420):566–568. [PubMed]
  • Marquardt O, Adam KH, Straub OC. Detection and localization of single-base sequence differences in foot-and-mouth disease virus genomes by the RNase mismatch cleavage method. J Virol Methods. 1991 Aug;33(3):267–282. [PubMed]
  • Mason PW, Baxt B, Brown F, Harber J, Murdin A, Wimmer E. Antibody-complexed foot-and-mouth disease virus, but not poliovirus, can infect normally insusceptible cells via the Fc receptor. Virology. 1993 Feb;192(2):568–577. [PubMed]
  • Mason PW, Rieder E, Baxt B. RGD sequence of foot-and-mouth disease virus is essential for infecting cells via the natural receptor but can be bypassed by an antibody-dependent enhancement pathway. Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1932–1936. [PMC free article] [PubMed]
  • Mateu MG. Antibody recognition of picornaviruses and escape from neutralization: a structural view. Virus Res. 1995 Sep;38(1):1–24. [PubMed]
  • Mateu MG, Hernández J, Martínez MA, Feigelstock D, Lea S, Pérez JJ, Giralt E, Stuart D, Palma EL, Domingo E. Antigenic heterogeneity of a foot-and-mouth disease virus serotype in the field is mediated by very limited sequence variation at several antigenic sites. J Virol. 1994 Mar;68(3):1407–1417. [PMC free article] [PubMed]
  • Mateu MG, Martínez MA, 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. [PMC free article] [PubMed]
  • McKenna TS, Lubroth J, Rieder E, Baxt B, Mason PW. Receptor binding site-deleted foot-and-mouth disease (FMD) virus protects cattle from FMD. J Virol. 1995 Sep;69(9):5787–5790. [PMC free article] [PubMed]
  • Meyer RF, Pacciarini M, Hilyard EJ, Ferrari S, Vakharia VN, Donini G, Brocchi E, Molitor TW. Genetic variation of foot-and-mouth disease virus from field outbreaks to laboratory isolation. Virus Res. 1994 Jun;32(3):299–312. [PubMed]
  • Patel M, Yanagishita M, Roderiquez G, Bou-Habib DC, Oravecz T, Hascall VC, Norcross MA. Cell-surface heparan sulfate proteoglycan mediates HIV-1 infection of T-cell lines. AIDS Res Hum Retroviruses. 1993 Feb;9(2):167–174. [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]
  • Rieder E, Baxt B, Mason PW. Animal-derived antigenic variants of foot-and-mouth disease virus type A12 have low affinity for cells in culture. J Virol. 1994 Aug;68(8):5296–5299. [PMC free article] [PubMed]
  • Rieder E, Baxt B, Lubroth J, Mason PW. Vaccines prepared from chimeras of foot-and-mouth disease virus (FMDV) induce neutralizing antibodies and protective immunity to multiple serotypes of FMDV. J Virol. 1994 Nov;68(11):7092–7098. [PMC free article] [PubMed]
  • Rieder E, Berinstein A, Baxt B, Kang A, Mason PW. Propagation of an attenuated virus by design: engineering a novel receptor for a noninfectious foot-and-mouth disease virus. Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10428–10433. [PMC free article] [PubMed]
  • Rieder E, Bunch T, Brown F, Mason PW. Genetically engineered foot-and-mouth disease viruses with poly(C) tracts of two nucleotides are virulent in mice. J Virol. 1993 Sep;67(9):5139–5145. [PMC free article] [PubMed]
  • Roivainen M, Piirainen L, Hovi T, Virtanen I, Riikonen T, Heino J, Hyypiä T. Entry of coxsackievirus A9 into host cells: specific interactions with alpha v beta 3 integrin, the vitronectin receptor. Virology. 1994 Sep;203(2):357–365. [PubMed]
  • Roivainen M, Hyypiä T, Piirainen L, Kalkkinen N, Stanway G, Hovi T. RGD-dependent entry of coxsackievirus A9 into host cells and its bypass after cleavage of VP1 protein by intestinal proteases. J Virol. 1991 Sep;65(9):4735–4740. [PMC free article] [PubMed]
  • Rueckert RR, Wimmer E. Systematic nomenclature of picornavirus proteins. J Virol. 1984 Jun;50(3):957–959. [PMC free article] [PubMed]
  • Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. [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]
  • 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]
  • WuDunn D, Spear PG. Initial interaction of herpes simplex virus with cells is binding to heparan sulfate. J Virol. 1989 Jan;63(1):52–58. [PMC free article] [PubMed]

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