1887

Abstract

Coxsackievirus A9 (CAV9) contains an arginine-glycine-aspartic acid (RGD) motif which participates in cell entry. Mutants with alterations in the RGD-containing region were utilized to explore the importance of the tripeptide in the pathogenesis of CAV9 in mice. Using hybridization, the parental CAV9 strain was observed to infect skeletal muscle (intercostal, platysma, lingual and thigh muscles) of newborn mice, whereas the RGD-less mutants were detectable only in platysma and lingual muscles. In addition, newborn mice infected with the mutants survived longer than CAV9-infected mice. In adult mice, the parental strain of CAV9, but not the mutants, achieved moderately high titres in the pancreas. These results suggest that the RGD motif has a significant role in the pathogenesis of CAV9 in mice but also that RGD-independent entry routes can be utilized in the infection of murine tissue.

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2003-09-01
2020-08-11
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References

  1. Acharya R., Fry E., Stuart D., Fox G., Rowlands D., Brown F.. 1989; The three-dimensional structure of foot-and-mouth disease virus at 2·9 Å resolution. Nature337:709–716
    [Google Scholar]
  2. Baranowski E., Ruiz-Jarabo C. M., Sevilla N., Andreu D., Beck E., Domingo E.. 2000; Cell recognition by foot-and-mouth disease virus that lacks the RGD integrin-binding motif: flexibility in apthovirus receptor usage. J Virol74:1641–1647
    [Google Scholar]
  3. Blaschuk K. L., Guerin C., Holland P. C.. 1997; Myoblast α V β 3 integrin levels are controlled by transcriptional regulation of expression of the β 3 subunit and down-regulation of β 3 subunit expression is required for skeletal muscle cell differentiation. Dev Biol184:266–277
    [Google Scholar]
  4. Boonyakiat Y., Hughes P. J., Ghazi F., Stanway G.. 2001; Arginine-glycine-aspartic acid motif is critical for human parechovirus 1 entry. J Virol75:10000–10004
    [Google Scholar]
  5. Buckley C. D., Pilling D., Henriquez N. V.. 7 other authors 1999; RGD peptides induce apoptosis by direct caspase-3 activation. Nature397:534–539
    [Google Scholar]
  6. Chang K. H., Auvinen P., Hyypiä T., Stanway G.. 1989; The nucleotide sequence of coxsackievirus A9: implications for receptor binding and enterovirus classification. J Gen Virol70:3269–3280
    [Google Scholar]
  7. Chang K. H., Day C., Walker J., Hyypiä T., Stanway G.. 1992; The nucleotide sequence of wild-type coxsackievirus A9 strains imply that an RGD motif in VP1 is functionally significant. J Gen Virol73:621–626
    [Google Scholar]
  8. Chiu C. Y., Mathias P., Nemerow G. R., Stewart P. L.. 1999; Structure of adenovirus complexed with its internalization receptor, α v β 5 integrin. J Virol73:6759–6768
    [Google Scholar]
  9. Forss S., Strebel K., Beck E., Schaller H.. 1984; Nucleotide sequence and genome organization of foot-and-mouth disease virus variant. Nucleic Acids Res12:6587–6601
    [Google Scholar]
  10. Fox G., Parry N. R., Barnett P. V., McGinn B., Rowlands D. J., Brown F.. 1989; The cell attachment site on foot-and-mouth disease virus includes the amino acid sequence RGD (arginine-glycine-aspartic acid). J Gen Virol70:625–637
    [Google Scholar]
  11. Grist N. R., Reid D.. 1988; General pathogenicity and epidemiology. In Coxsackieviruses, A General Update pp 221–239 Edited by Berdinelli M., Friedman H.. New York: Plenum;
    [Google Scholar]
  12. Harvala H., Kalimo H., Dahllund L., Santti J., Hughes P., Hyypiä T., Stanway G.. 2002; Mapping of tissue tropism determinants in coxsackievirus genomes. J Gen Virol83:1697–1706
    [Google Scholar]
  13. Hovi T., Stenvik M., Rosenlew M.. 1996; Relative abundance of enterovirus serotypes in sewage differs from that in patients: clinical and epidemiological implications. Epidemiol Infect116:91–97
    [Google Scholar]
  14. Hughes P. J., Horsnell C., Hyypiä T., Stanway G.. 1995; The coxsackievirus A9 RGD motif is not essential for virus viability. J Virol69:8035–8040
    [Google Scholar]
  15. Hyypiä T., Horsnell M., Maaronen M., Khan M., Kalkkinen N., Auvinen P., Kinnunen L., Stanway G.. 1992; A distinct picornavirus group identified by sequence analysis. Proc Natl Acad Sci U S A89:8847–8851
    [Google Scholar]
  16. Hyypiä T., Kallajoki M., Maaronen M., Stanway G., Kandolf R., Auvinen P., Kalimo H.. 1993; Pathogenetic differences between coxsackie A and B virus infections in newborn mice. Virus Res27:71–78
    [Google Scholar]
  17. Jackson T., Blakemore W., Newman J. W. I., Knowles N. J., Mould A. P., Humphries M. J., King A. M. Q.. 2000a; Foot-and-mouth disease virus is a ligand for the high-affinity binding conformation of integrin α 5 β 1: influence of the leucine residue within the RGDL motif on selectivity of integrin binding. J Gen Virol81:1383–1391
    [Google Scholar]
  18. Jackson T., Sheppard D., Denyer M., Blakemore W., King A. M. Q.. 2000b; The epithelial integrin α V β 6 is a receptor for foot-and-mouth disease virus. J Virol74:4949–4956
    [Google Scholar]
  19. Menko A. S., Boettiger D.. 1987; Occupation of the extracellular matrix receptor, integrin, is a control point myogenic differentiation. Cell51:51–57
    [Google Scholar]
  20. Neff S., Sá-Carvalho D., Rieder E., Mason P. W., Blystone S. D., Brown E. J., Baxt B.. 1998; Foot-and-mouth disease virus virulent for cattle utilizes the integrin α V β 3 as its receptor. J Virol72:3587–3594
    [Google Scholar]
  21. Nelsen-Salz B., Eggers H. J., Zimmermann H.. 1999; Integrin α V β 3 (vitronectin receptor) is a candidate receptor for the virulent echovirus 9 strain Barty. J Gen Virol80:2311–2313
    [Google Scholar]
  22. Paananen A., Ylipaasto P., Rieder E., Hovi T., Galama J., Roivainen M.. 2003; Molecular and biological analysis of echovirus 9 strain isolated from a diabetic child. J Med Virol69:529–537
    [Google Scholar]
  23. Pulli T., Lankinen H., Roivainen M., Hyypiä T.. 1998a; Antigenic sites of coxsackievirus A9. Virology240:202–212
    [Google Scholar]
  24. Pulli T., Roivainen M., Hovi T., Hyypiä T.. 1998b; Induction of neutralizing antibodies by synthetic peptides representing the C terminus of coxsackievirus A9 capsid protein VP1. J Gen Virol79:2249–2253
    [Google Scholar]
  25. Roivainen M., Hyypiä T., Piirainen L., Kalkkinen N., Stanway G., Hovi T.. 1991; RGD-dependent entry of coxsackievirus A9 into host cell and its bypass after cleavage of VP1 protein by intestinal proteases. J Virol65:4735–4740
    [Google Scholar]
  26. Roivainen M., Piirainen L., Hovi T., Virtanen I., Riikonen T., Heino J., Hyypiä T.. 1994; Entry of coxsackievirus A9 into host cells: specific interactions with α v β 3 integrin, the vitronectin receptor. Virology203:357–365
    [Google Scholar]
  27. Ruoslahti E., Reed J.. 1999; New way to activate caspases. Nature397:479–480
    [Google Scholar]
  28. Santti J., Harvala H., Kinnunen L., Hyypiä T.. 2000; Molecular epidemiology and evolution of coxsackievirus A9. J Gen Virol81:1361–1372
    [Google Scholar]
  29. Stanway G., Kalkkinen N., Roivainen M., Ghazi F., Khan M., Smyth M., Meurman O., Hyypiä T.. 1994; Molecular and biological characteristics of echovirus 22, a representative of a new picornavirus group. J Virol68:8232–8238
    [Google Scholar]
  30. Triantafilou M., Triantafilou K., Wilson K. M., Takada Y., Fernandez N.. 2000; High affinity interactions of coxsackievirus A9 with integrin α V β 3 (CD51/61) require the CYDMKTTC sequence of β 3, but do not require the RGD sequence of the CAV-9 VP1 protein. Hum Immunol61:453–459
    [Google Scholar]
  31. Zimmermann H., Eggers H. J., Nelsen-Salz B.. 1996; Molecular cloning and sequence determination of the complete genome of the virulent echovirus 9 strain Barty. Virus Genes12:149–154
    [Google Scholar]
  32. Zimmermann H., Eggers H. J., Nelsen-Salz B.. 1997; Cell attachment and mouse virulence of echovirus 9 correlate with an RGD motif in the capsid protein VP1. Virology233:149–156
    [Google Scholar]
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