Efficient Neutralization of Foot-and-mouth Disease Virus by Monovalent Antibody Binding

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 1997 Nov 26

PMID 9371652

Citations 3

Authors

N Verdaguer

I Fita

E Domingo

M G Mateu

Affiliations

Soon will be listed here.

Abstract

Neutralization of an aphthovirus by monovalent binding of an antibody is reported. Foot-and-mouth disease virus (FMDV) clone C-S8c1 was neutralized by monoclonal antibody (MAb) SD6, which was directed to a continuous epitope within a major antigenic site of the G-H loop of capsid protein VP1. On a molar basis, the Fab fragment was at most fivefold less active in neutralization than the intact antibody, and both blocked virus attachment to cells. Neither the antibody nor the Fab fragment caused aggregation of virions, as evidenced by sucrose gradient sedimentation studies of the antibody-virus complex formed at antibody to virion ratios of 1:50 to 1:10,000. The results of neutralization of infectivity and of ultracentrifugation are fully consistent with structural data based on X-ray crystallographic and cryoelectron microscopy studies, which showed monovalent interaction of the antibody with a critical receptor binding motif Arg-Gly-Asp. The conclusions of these neutralization studies are that (i) bivalent binding of antibody is not a requisite for strong neutralization of aphthoviruses and (ii) aggregation of viral particles, which has been proposed to be the dominant neutralization mechanism of antibodies that bind monovalently to virions, is not necessary for the neutralization of FMDV C-S8c1 by MAb SD6.

Citing Articles

Deletion mutants of VPg reveal new cytopathology determinants in a picornavirus.

Arias A, Perales C, Escarmis C, Domingo E PLoS One. 2010; 5(5):e10735.

PMID: 20505767 PMC: 2873979. DOI: 10.1371/journal.pone.0010735.

Hidden virulence determinants in a viral quasispecies in vivo.

Sanz-Ramos M, Diaz-San Segundo F, Escarmis C, Domingo E, Sevilla N J Virol. 2008; 82(21):10465-76.

PMID: 18715925 PMC: 2573215. DOI: 10.1128/JVI.00825-08.

Verdaguer N, Sevilla N, Valero M, Stuart D, Brocchi E, Andreu D J Virol. 1998; 72(1):739-48.

PMID: 9420281 PMC: 109430. DOI: 10.1128/JVI.72.1.739-748.1998.

References

Wild T, Brown F . Nature of the inactivating action of trypsin on foot-and-mouth disease virus. J Gen Virol. 1967; 1(2):247-50. DOI: 10.1099/0022-1317-1-2-247. View

Martinez M, Verdaguer N, Mateu M, Domingo E . Evolution subverting essentiality: dispensability of the cell attachment Arg-Gly-Asp motif in multiply passaged foot-and-mouth disease virus. Proc Natl Acad Sci U S A. 1997; 94(13):6798-802. PMC: 21238. DOI: 10.1073/pnas.94.13.6798. View

Sobrino F, Davila M, Ortin J, Domingo E . Multiple genetic variants arise in the course of replication of foot-and-mouth disease virus in cell culture. Virology. 1983; 128(2):310-8. DOI: 10.1016/0042-6822(83)90258-1. View

Baxt B, MORGAN D, Robertson B, Timpone C . Epitopes on foot-and-mouth disease virus outer capsid protein VP1 involved in neutralization and cell attachment. J Virol. 1984; 51(2):298-305. PMC: 254438. DOI: 10.1128/JVI.51.2.298-305.1984. View

Wetz K, Willingmann P, Zeichhardt H, HABERMEHL K . Neutralization of poliovirus by polyclonal antibodies requires binding of a single IgG molecule per virion. Arch Virol. 1986; 91(3-4):207-20. DOI: 10.1007/BF01314281. View

Mateu M, Rocha E, Vicente O, Vayreda F, Navalpotro C, Andreu D . Reactivity with monoclonal antibodies of viruses from an episode of foot-and-mouth disease. Virus Res. 1987; 8(3):261-74. DOI: 10.1016/0168-1702(87)90020-7. View

Colonno R, Callahan P, Leippe D, Rueckert R, Tomassini J . Inhibition of rhinovirus attachment by neutralizing monoclonal antibodies and their Fab fragments. J Virol. 1989; 63(1):36-42. PMC: 247654. DOI: 10.1128/JVI.63.1.36-42.1989. View

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; 337(6209):709-16. DOI: 10.1038/337709a0. View

Fox G, Parry N, Barnett P, McGinn B, Rowlands D, 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; 70 ( Pt 3):625-37. DOI: 10.1099/0022-1317-70-3-625. View

10.

Mateu M, Martinez M, Rocha E, Andreu D, Parejo J, Giralt 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; 86(15):5883-7. PMC: 297735. DOI: 10.1073/pnas.86.15.5883. View

11.

Parry N, Fox G, Rowlands D, Brown F, Fry E, Acharya R . Structural and serological evidence for a novel mechanism of antigenic variation in foot-and-mouth disease virus. Nature. 1990; 347(6293):569-72. DOI: 10.1038/347569a0. View

12.

Martinez M, Carrillo C, Gonzalez-Candelas F, Moya A, Domingo E, Sobrino F . Fitness alteration of foot-and-mouth disease virus mutants: measurement of adaptability of viral quasispecies. J Virol. 1991; 65(7):3954-7. PMC: 241436. DOI: 10.1128/JVI.65.7.3954-3957.1991. View

13.

Mccullough K, De Simone F, Brocchi E, Capucci L, Crowther J, Kihm U . Protective immune response against foot-and-mouth disease. J Virol. 1992; 66(4):1835-40. PMC: 288969. DOI: 10.1128/JVI.66.4.1835-1840.1992. View

14.

Domingo E, Escarmis C, Martinez M, Martinez-Salas E, Mateu M . Foot-and-mouth disease virus populations are quasispecies. Curr Top Microbiol Immunol. 1992; 176:33-47. DOI: 10.1007/978-3-642-77011-1_3. View

15.

Smith T, Olson N, Cheng R, Liu H, Chase E, Lee W . Structure of human rhinovirus complexed with Fab fragments from a neutralizing antibody. J Virol. 1993; 67(3):1148-58. PMC: 237479. DOI: 10.1128/JVI.67.3.1148-1158.1993. View

16.

Logan D, ABU-GHAZALEH R, Blakemore W, Curry S, Jackson T, King A . Structure of a major immunogenic site on foot-and-mouth disease virus. Nature. 1993; 362(6420):566-8. DOI: 10.1038/362566a0. View

17.

Smith T, Olson N, Cheng R, Chase E, Baker T . Structure of a human rhinovirus-bivalently bound antibody complex: implications for viral neutralization and antibody flexibility. Proc Natl Acad Sci U S A. 1993; 90(15):7015-8. PMC: 47066. DOI: 10.1073/pnas.90.15.7015. View

18.

Novella I, Borrego B, Mateu M, Domingo E, Giralt E, Andreu D . Use of substituted and tandem-repeated peptides to probe the relevance of the highly conserved RGD tripeptide in the immune response against foot-and-mouth disease virus. FEBS Lett. 1993; 330(3):253-9. DOI: 10.1016/0014-5793(93)80883-v. View

19.

Mason P, 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; 91(5):1932-6. PMC: 43278. DOI: 10.1073/pnas.91.5.1932. View

20.

Verdaguer N, Mateu M, Bravo J, Tormo J, Giralt E, Andreu D . Crystallization and preliminary X-ray diffraction studies of a monoclonal antibody Fab fragment against foot-and-mouth disease virus and of its complex with the main antigenic site peptide. Proteins. 1994; 18(2):201-3. DOI: 10.1002/prot.340180212. View