1887

Abstract

A total of 38 neutralization escape mutant viruses have been selected from a cloned stock of human rhinovirus serotype 2 (HRV-2), using either of two monoclonal antibodies (MAbs) which recognize overlapping epitopes as judged by competition binding. The mutant viruses were analysed for their sensitivity to a panel of antiviral MAbs by antibody binding and virus neutralization assays. The position and nature of the selected mutations was determined by sequencing of the virus RNAs, and the location of the substituted amino acids on the three-dimensional structure of the virus predicted from the co-ordinates determined for the closely related HRV-1A. Escape from neutralization could be attributed to single amino acid substitutions in all but one case, which had a deletion of four amino acids. In all cases in which the same mutation was found more than once, these mutations were transitions. The ratio of transition to transversion mutations was about 5:1 overall or about 1·7:1 if only unique substitutions are considered. Each antibody selected for a discrete cluster of mutations and the area of these clusters was considerably less than that determined to be in contact with antibodies from X-ray crystallographic analyses of antibody/protein complexes. One mutation did not occur within the cluster of others selected with the same antibody. This substitution occurred at the base of a small loop and may cause conformational changes at the virus surface.

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1993-02-01
2022-09-25
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References

  1. Air G. M., Laver W. G., Webster R. G. 1990; Mechanism of antigenic variation in an individual epitope on influenza virus neuraminidase. Journal of Virology 64:5797–5803
    [Google Scholar]
  2. Amit A. G., Mariuzza R. A., Phillips S. E. V., Poljak R. G. 1986; Three dimensional structure of an antigen-antibody complex at 2—8 A resolution. Science 223:747–753
    [Google Scholar]
  3. Appleyard G., Russell S. M., Clarke B. E., Speller S. A., Trowbridge M., Vadolas J. 1990; Neutralization epitopes on human rhinovirus type 2. Journal of General Virology 71:1275–1282
    [Google Scholar]
  4. Caton A. J., Brownlee G. G., Yewdell T., Gerhard W. 1982; The antigenic structure of the influenza virus A/PR/8/34 hemagglutinin (Hl-subtype). Cell 31:417–427
    [Google Scholar]
  5. Colman P. M., Laver W. G-, Varghese J. N., Baker A. T., Tulloch P. A., Air G. M., Webster R. G. 1987; Three dimensional structure of a complex of antibody with influenza virus neuraminidase. Nature, London 326:358–363
    [Google Scholar]
  6. Getzoff E. D., Geysen H. M., Stuart J. R., Alexander H., Tainer J. A., Lerner R. A. 1987; Mechanisms of antibody binding to a protein. Science 235:1191–1196
    [Google Scholar]
  7. Geysen H. M., Meloen R. H., Barteling S. J. 1984; Use of peptide synthesis to probe viral antigens for epitopes to a resolution of a single amino acid. Proceedings of the National Academy of Sciences, U.S.A. 813998–4002
    [Google Scholar]
  8. Johnson D., Gautsch J., Sportsman J., Elder J. 1984; Improved technique utilizing non-fat dry milk for analysis of proteins and nucleic acids transferred to nitrocellulose. Gene Analysis Techniques 1:3–8
    [Google Scholar]
  9. Jones A. 1985; Interactive computer graphics Frodo. Methods in Enzymology 115:157–171
    [Google Scholar]
  10. Kim S., Smith T. J., Chapman M. S., Rossmann M. G., Pevear D. C., Dutko F. J-, Felock P. J., Diana G. D., McKinlay M. A. 1989; The crystal structure of human rhinovirus serotype 1A (HRV1A). Journal of Molecular Biology 210:91–111
    [Google Scholar]
  11. Laemmli U. K. 1970; Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, London 227:680–685
    [Google Scholar]
  12. McCullough K. C-, Crowther J. R., Butcher R. N. 1985; Alteration in antibody reactivity with foot and mouth disease virus (FMDV) 146S antigen before and after binding to a solid phase or completing with specific antibody. Journal of Immunological Methods 82:91–100
    [Google Scholar]
  13. Mariuzza R. A., Phillips S. E. V., Poljak R. G. 1987; The structural basis of antigen antibody recognition. Annual Review of Biophysics and Biophysical Chemistry 16:139–159
    [Google Scholar]
  14. Milich D. R. 1989; Synthetic T and B cell recognition sites: implications for vaccine development. Advances in Immunology 45:195–282
    [Google Scholar]
  15. Page G. S., Mosser A. G., Hogle J. M., Filman D. J., Rueckert R. R., Chow M. 1988; Three dimensional structure of poliovirus serotype 1 neutralizing determinants. Journal of Virology 62:1781–1794
    [Google Scholar]
  16. Parry N. R-, Ouldridge E. J., Barnett P., Clarke B. E., Francis M. J., Fox J. D., Rowlands D. J., Brown F. 1989; Serological prospects for peptide vaccines against foot-and-mouth disease virus. Journal of General Virology 70:2919–2930
    [Google Scholar]
  17. Reynolds C., Birnby D., Chow M. 1992; Folding and processing of the capsid protein precursor PI is kinetically retarded in neutralization site 3B mutants of poliovirus. Journal of Virology 66:1641–1648
    [Google Scholar]
  18. Rossmann M. G-, Arnold E., Erickson J. W., Frankenbergber E. A., Griffith J. P., Hecht H.-J., Johnson J. E., Kamer G., Luo M., Mosser A. G., Rueckert R. R., Sherry B., Vriend G. 1985; Structure of a human common cold virus and functional relationship to other picornaviruses. Nature, London 317:145–153
    [Google Scholar]
  19. Sheriff S., Silverton E. W., Padlar E. A., Cohen G. A., Smith-Gill S. J., Finzel B. C., Davies D. R. 1987; Three dimensional structure of an antibody—antigen complex. Proceedings of the National Academy of Sciences 848075–8079
    [Google Scholar]
  20. Sherry B., Rueckert R. R. 1985; Evidence for at least two dominant neutralization antigens on human rhinoviruses. Journal of Virology 53:137–143
    [Google Scholar]
  21. Towbin H., Staehelin T., Gordon J. 1979; Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proceedings ofthe National Academy of Sciences, U.S.A 764350–4354
    [Google Scholar]
  22. Wiley D. C., Skehel J. J. 1987; The structure and function of the hemagglutinin membrane glycoprotein of influenza virus. Annual Review of Biochemistry 56:365–394
    [Google Scholar]
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