• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jvirolPermissionsJournals.ASM.orgJournalJV ArticleJournal InfoAuthorsReviewers
J Virol. Feb 1997; 71(2): 1046–1051.
PMCID: PMC191155

Point mutations within the betaG-betaH loop of foot-and-mouth disease virus O1K affect virus attachment to target cells.


The amino acid sequence Arg-Gly-Asp (RGD) is a highly conserved region located on the P1D protein of most sero- and subtypes of foot-and-mouth disease virus (FMDV)and participates in binding of FMDV to their target cells. In order to analyze the role of the RGD sequence in FMDV infection of cells in more detail, 13 mutations within or near the RGD sequence of virus type O1Kaufbeuren were designed by using a full-length cDNA plasmid. Transfection of baby hamster kidney cells (BHK-21) with in vitro-transcribed cRNAs containing mutations bordering the RGD sequence led to the production of infectious virus in most cases. In contrast, almost all of the mutants containing changes within the RGD sequence produced noninfectious viral particles indistinguishable from wild-type virus by electron microscopy. In order to demonstrate that these noninfectious progeny from the RGD mutants were defective only in their cell adsorption, the respective cRNAs were cotransfected together with a cRNA expressing the wild-type P1 protein. The resulting virus particles were able to infect BHK-21 cells. These results demonstrate the important role of the RGD sequence in FMDV binding to cells but also emphasize the influence of other amino acids in the bordering region.

Full Text

The Full Text of this article is available as a PDF (330K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • 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]
  • Akiyama SK, Yamada KM. Synthetic peptides competitively inhibit both direct binding to fibroblasts and functional biological assays for the purified cell-binding domain of fibronectin. J Biol Chem. 1985 Sep 5;260(19):10402–10405. [PubMed]
  • Amadori M, Berneri C, Archetti IL. Immunogenicity of foot-and-mouth disease virus grown in BHK-21 suspension cells. Correlation with cell ploidy alterations and abnormal expression of the alpha 5 beta 1 integrin. Vaccine. 1994 Feb;12(2):159–166. [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]
  • Baxt B, Bachrach HL. Early interactions of foot-and-mouth disease virus with cultured cells. Virology. 1980 Jul 15;104(1):42–55. [PubMed]
  • Berglund P, Sjöberg M, Garoff H, Atkins GJ, Sheahan BJ, Liljeström P. Semliki Forest virus expression system: production of conditionally infectious recombinant particles. Biotechnology (N Y) 1993 Aug;11(8):916–920. [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]
  • Brooksby JB. Portraits of viruses: foot-and-mouth disease virus. Intervirology. 1982;18(1-2):1–23. [PubMed]
  • Carroll AR, Rowlands DJ, Clarke BE. The complete nucleotide sequence of the RNA coding for the primary translation product of foot and mouth disease virus. Nucleic Acids Res. 1984 Mar 12;12(5):2461–2472. [PMC free article] [PubMed]
  • Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. [PubMed]
  • Dente L, Cesareni G, Cortese R. pEMBL: a new family of single stranded plasmids. Nucleic Acids Res. 1983 Mar 25;11(6):1645–1655. [PMC free article] [PubMed]
  • Forss S, Schaller H. A tandem repeat gene in a picornavirus. Nucleic Acids Res. 1982 Oct 25;10(20):6441–6450. [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]
  • Fricks CE, Hogle JM. Cell-induced conformational change in poliovirus: externalization of the amino terminus of VP1 is responsible for liposome binding. J Virol. 1990 May;64(5):1934–1945. [PMC free article] [PubMed]
  • Hayman EG, Pierschbacher MD, Ruoslahti E. Detachment of cells from culture substrate by soluble fibronectin peptides. J Cell Biol. 1985 Jun;100(6):1948–1954. [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]
  • 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]
  • Humphries MJ, Akiyama SK, Komoriya A, Olden K, Yamada KM. Identification of an alternatively spliced site in human plasma fibronectin that mediates cell type-specific adhesion. J Cell Biol. 1986 Dec;103(6 Pt 2):2637–2647. [PMC free article] [PubMed]
  • Hynes RO. Integrins: versatility, modulation, and signaling in cell adhesion. Cell. 1992 Apr 3;69(1):11–25. [PubMed]
  • JOKLIK WK, DARNELL JE., Jr The adsorption and early fate of purified poliovirus in HeLa cells. Virology. 1961 Apr;13:439–447. [PubMed]
  • Krieg PA, Melton DA. In vitro RNA synthesis with SP6 RNA polymerase. Methods Enzymol. 1987;155:397–415. [PubMed]
  • Laporte J, Grosclaude J, Wantyghem J, Bernard S, Rouzé P. Neutralisation en culture cellulaire du pouvoir infectieuz du virus de la fièvre aphteuse par des sérums provenant de porcs immunisés à l'aide d'une protéine virale purifiée. C R Acad Sci Hebd Seances Acad Sci D. 1973 Jun 18;276(25):3399–3401. [PubMed]
  • Liljeström P, Garoff H. A new generation of animal cell expression vectors based on the Semliki Forest virus replicon. Biotechnology (N Y) 1991 Dec;9(12):1356–1361. [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]
  • 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, Valero ML, Andreu D, Domingo E. Systematic replacement of amino acid residues within an Arg-Gly-Asp-containing loop of foot-and-mouth disease virus and effect on cell recognition. J Biol Chem. 1996 May 31;271(22):12814–12819. [PubMed]
  • Parry N, Fox G, Rowlands D, Brown F, Fry E, Acharya R, Logan D, Stuart D. Structural and serological evidence for a novel mechanism of antigenic variation in foot-and-mouth disease virus. Nature. 1990 Oct 11;347(6293):569–572. [PubMed]
  • Pfaff E, Mussgay M, Böhm HO, Schulz GE, Schaller H. Antibodies against a preselected peptide recognize and neutralize foot and mouth disease virus. EMBO J. 1982;1(7):869–874. [PMC free article] [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]
  • 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]
  • Ruoslahti E, Pierschbacher MD. New perspectives in cell adhesion: RGD and integrins. Science. 1987 Oct 23;238(4826):491–497. [PubMed]
  • Ruoslahti E. Integrins. J Clin Invest. 1991 Jan;87(1):1–5. [PMC free article] [PubMed]
  • Sangar DV, Black DN, Rowlands DJ, Brown F. Biochemical mapping of the foot-and-mouth disease virus genome. J Gen Virol. 1977 May;35(2):281–297. [PubMed]
  • Sangar DV. The replication of picornaviruses. J Gen Virol. 1979 Oct;45(1):1–13. [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [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]
  • Tamkun JW, DeSimone DW, Fonda D, Patel RS, Buck C, Horwitz AF, Hynes RO. Structure of integrin, a glycoprotein involved in the transmembrane linkage between fibronectin and actin. Cell. 1986 Jul 18;46(2):271–282. [PubMed]
  • Wagner GG, Card JL, Cowan KM. Immunochemical studies of foot-and-mouth disease. VII. Characterization of foot-and-mouth disease virus concentrated by polyethylene glycol precipitation. Arch Gesamte Virusforsch. 1970;30(4):343–352. [PubMed]
  • Yamada KM, Olden K. Fibronectins--adhesive glycoproteins of cell surface and blood. Nature. 1978 Sep 21;275(5677):179–184. [PubMed]
  • Zibert A, Maass G, Strebel K, Falk MM, Beck E. Infectious foot-and-mouth disease virus derived from a cloned full-length cDNA. J Virol. 1990 Jun;64(6):2467–2473. [PMC free article] [PubMed]
  • Zoller MJ, Smith M. Oligonucleotide-directed mutagenesis: a simple method using two oligonucleotide primers and a single-stranded DNA template. Methods Enzymol. 1987;154:329–350. [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...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...