1887

Abstract

Summary

Antigenic variation of the neuraminidase of A/H3N2 influenza viruses may be associated with modifications of the catalytic activity of this enzyme. We observed this phenomenon when studying two prototype strains: A/Hong Kong/1/68 (X31K) and A/Bangkok/2/79. For the neuraminidases of these strains, we determined their substrate specificity, initial velocity, optimum pH, optimum temperature, heat inactivation and Michaelis constants and their inactivation by chemical group-specific reagents. In order to examine the relationship between antigenic variation and enzyme activity of the influenza neuraminidases, three X31K monoclonal variants were selected using anti-neuraminidase monoclonal antibodies. Two of these (X31/NC92 and X31/NC56) were modified at a single neuraminidase epitope, and the third one (X31/NC92/NC56) at two epitopes. The neuraminidase activity of the monoclonal variants was analysed and compared to that of the prototype strains. Compared to A/Hong Kong/1/68, the A/Bangkok/2/79 strain neuraminidase was more susceptible to inactivation by physical (pH, temperature) and chemical agents [urea, dithiothreitol, 1-ethyl-3-(3-dimethylaminopropyl carbodiimide), iodoacetamide, acetic anhydride, 2, 3-butanedione] and showed a twofold lower substrate affinity for -acetylneuraminlactose. The neuraminidase activity of the monoclonal variants of X31K became more susceptible to inactivation by both physical and chemical agents than the original strain and exhibited various substrate affinities. Therefore, we conclude that the enzymic properties of the structurally conserved active sites of the neuraminidase molecule may be influenced by antigenic modifications that affect the variable areas of the neuraminidase and that the degree of this enzymic variation is related to the nature and number of the modified epitope(s). A local conformational change in the neuraminidase molecule reflected as antigenic variation could be involved in modification of enzyme activity.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-67-3-409
1986-03-01
2022-01-24
Loading full text...

Full text loading...

/deliver/fulltext/jgv/67/3/JV0670030409.html?itemId=/content/journal/jgv/10.1099/0022-1317-67-3-409&mimeType=html&fmt=ahah

References

  1. Aymard-henry M., Coleman M. T., Dowdle W. R., Laver W. G., Schild G. C., Webster R. G. 1973; Influenza virus neuraminidase and neuraminidase-inhibition test procedures. Bulletin of the World Health Organization 48:199–202
    [Google Scholar]
  2. Bucher D., Palese P. 1975; The biologically active proteins of influenza virus: neuraminidase. In The Influenza Viruses and Influenza pp. 83–123 Edited by Kilbourne E. D. New York: Academic Press;
    [Google Scholar]
  3. Colman P. M., Ward C. W. 1985; Structure and diversity of influenza virus neuraminidase. Current Topics in Microbiology and Immunology 114:178–255
    [Google Scholar]
  4. Colman P. M., Varghese J. N., Laver W. G. 1983; Structure of the catalytic and antigenic sites in influenza virus neuraminidase. Nature, London 303:41–44
    [Google Scholar]
  5. Davenport F. M. 1976; Influenza virus. In Viral Infections in Humans pp. 273–296 Edited by Evans A. S. New York: Plenum Press;
    [Google Scholar]
  6. Dimmock N. J. 1971; Dependence of the activity of an influenza virus neuraminidase upon Ca2+. Journal of General Virology 13:481–483
    [Google Scholar]
  7. Drzeniek R. 1972; Viral and bacterial neuraminidases. Current Topics in Microbiology and Immunology 59:35–74
    [Google Scholar]
  8. Gerhard W., Webster R. G. 1978; Antigenic drift in influenza A viruses. I. Selection and characterization of antigenic variants of A/PR/8/34 (H0N 1) influenza virus with monoclonal antibodies. Journal of Experimental Medicine 148:383–392
    [Google Scholar]
  9. Kabayo J. P., Hutchinson D. W. 1977; Studies on a neuraminidase from Streptomyces griseus. FEBS Letters 78:221–224
    [Google Scholar]
  10. Kessler N., Suiphon E., Aymard M. 1982; Intérêtde la méthode ELISA appliquée au diagnostic des infections à Paramyxovirus. Coopération franco-sovietique, 4éme colloque sur la grippe, Editions I. N. S. E. R. M., Paris pp. 45–60
    [Google Scholar]
  11. Knossow M., Daniels R. S., Douglas A. R., Skehel J. J., Wiley D. C. 1984; Three-dimensional structure of an antigenic mutant of the influenza virus haemagglutinin. Nature, London 311:678–680
    [Google Scholar]
  12. Laver W. G., Air G. M., Webster R. G., Gerhard W., Ward C. W., Dopheide T. A. A. 1979; Antigenic drift in type A influenza virus: sequence differences in the hemagglutinin of Hong Kong (H3N2) variants selected with monoclonal hybridoma antibodies. Virology 98:226–237
    [Google Scholar]
  13. Lentz M. R., Air G. M., Laver W. G., Webster R. G. 1984; Sequence of the neuraminidase gene of influenza virus A/Tokyo/3/67 and previously uncharacterized monoclonal variants. Virology 135:257–265
    [Google Scholar]
  14. Lowry O. H., Rosebrough N. J., Farr A. L., Randall R. J. 1951; Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry 193:265–275
    [Google Scholar]
  15. Palese P., Tobika K., Masahiro U., Compans R. W. 1974; Characterization of temperature sensitive influenza virus mutants defective in neuraminidase. Virology 61:397–410
    [Google Scholar]
  16. Palmer D. F., Dowdle W. R., Coleman M. T., Schild G. C. 1975; Haemagglutination-inhibition test. In Advanced Laboratory Techniques for Immunological Diagnosis pp. 25–62 U.S. Department of Health Immunology Series no. 6, Procedural Guide, part 2 Atlanta: U.S. Public Health Service;
    [Google Scholar]
  17. Paniker C. K. J. 1968; Serological relationships between the neuraminidases of influenza viruses. Journal of General Virology 2:385–394
    [Google Scholar]
  18. Rafelson M. E., Schneir M., Wilson V. W. 1963; Studies on the neuraminidase of influenza virus. II. Additional properties of the enzyme from the avian and PR 8 strains. Archives of Biochemistry and Biophysics 103:424–430
    [Google Scholar]
  19. Voller A., Bidwell D., Bartlett A. 1976; Microplate enzyme immunoassays for immunodiagnosis of virus infections. In Manual of Clinical Immunology pp. 506–512 Edited by Rose N., Friedman H. Washington, D.C.: American Society for Microbiology;
    [Google Scholar]
  20. Webster R. G., Laver W. G. 1975; Antigenic variation of influenza viruses. In The Influenza Viruses and Influenza pp. 269–314 Edited by Kilbourne E. D. New York: Academic Press;
    [Google Scholar]
  21. Webster R. G., Laver W. G., Air G. M., Schild G. C. 1982; Molecular mechanisms of variation in influenza viruses. Nature, London 296:115–121
    [Google Scholar]
  22. Webster R. G., Brown L. E., Laver W. G. 1984; Antigenic and biological characterization of influenza virus neuraminidase (N2) with monoclonal antibodies. Virology 135:30–42
    [Google Scholar]
  23. Weekly Epidemiological Record, WHO 1980 Influenza Surveillance 55: p 158
    [Google Scholar]
  24. Weekly Epidemiological Record, WHO 1981 Influenza in the World, October 1979–September 1980 56: pp. 33–37
    [Google Scholar]
  25. Weekly Epidemiological Record, WHO 1982 Influenza in the World, October 1980-September 1981 57: pp. 4145
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-67-3-409
Loading
/content/journal/jgv/10.1099/0022-1317-67-3-409
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error