Virus Genes

, Volume 10, Issue 3, pp 253–260 | Cite as

Changes in the neuraminidase of neurovirulent influenza virus strains



The influenza virus A/WS/33 has been adapted to mouse brain to produce two neurovirulent derivatives, A/NWS/33 (NWS) and A/WSN/33 (WSN), with the viral neuraminidase gene shown to be the major determinant of neurovirulence. The complete nucleotide sequence of the NA genes from each strain has been determined, which has allowed the identification of changes that have occurred during adaptation to mouse brain. Five changes are shared by the neurovirulent strains. Comparison to the known neuraminidase structure has identified four of these that may affect the active site of the enzyme. In addition, significant differences in the properties of the neuraminidase from the neurovirulent strains were observed relative to the parent strain. While no correlation was observed between neurovirulence and overall neuraminidase activity or preference for a particularN-substitution, the enzymes from both neurovirulent strains showed an increased preference for small substrates and those with 2→3 linkages, and their activity was potentiated by Ca2+ ions.

Key words

influenza A viruses neurovirulence NA gene 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Stuart-Harris C.H., Lancet1 497–499, 1939.Google Scholar
  2. 2.
    Francis T. and Moore A.E., J Exp Med72 717–728, 1940.Google Scholar
  3. 3.
    Kilbourne E.D., Progr Med Virol5 79–126, 1963.Google Scholar
  4. 4.
    Hobson N., Flockton H.I., and Gould E.A., J Gen Virol3 445–448, 1968.Google Scholar
  5. 5.
    Mayer V., Shulman J.L., and Kilbourne E.D., J Virol11 272–278, 1973.Google Scholar
  6. 6.
    Sugiura A. and Ueda M., Virology101 440–449, 1980.Google Scholar
  7. 7.
    Nakajima S. and Sugiura A., Virology101 450–457, 1980.Google Scholar
  8. 8.
    Colman P.M. in Krug R.M. (ed).The Influenza Viruses. Plenum Press, New York, 1989, pp. 175–218.Google Scholar
  9. 9.
    Ghendon Y., Tukova E., Vonka V., Klimov A., Ginzburg V., and Markushin S., J Gen Virol44 179–186, 1979.Google Scholar
  10. 10.
    Schulman J.L. and Palese P., J Virol24 170–176, 1977.Google Scholar
  11. 11.
    Hiti A.L., and Nayak D.P., J Virol41 730–734, 1982.Google Scholar
  12. 12.
    Enami M. and Palese P., J Virol65 2711–2713, 1991.Google Scholar
  13. 13.
    Fields S., Winter G., and Brownlee G.G., Nature290 213–217, 1981.Google Scholar
  14. 14.
    Ward A.C., Azad A.A., and McKimm-Breschkin J.L., Virus Genes10 91–94, 1995.Google Scholar
  15. 15.
    Barrett T. and Inglis S.C. in Mahy B.W.J. (ed).Virology: A Practical Approach. IRL Press, London, 1985, pp. 119–150.Google Scholar
  16. 16.
    Varghese J.N. and Colman P.M. J Mol Biol221 473–486, 1991.Google Scholar
  17. 17.
    Varghese J.N., McKimm-Breschkin J.L., Caldwell J.B., Kortt A.A., and Colman P.M., Protein Struct Funct Genet14 327–332, 1992.Google Scholar
  18. 18.
    Kraulis P.J. J Appl Crystallogr24 946–950, 1991.Google Scholar
  19. 19.
    Green E.D., Adelt G., Baenziger J.U., Wilson S., and Van Halbeek H., J Biol Chem263 18253–18268, 1988.Google Scholar
  20. 20.
    Martensson E., Raal A., and Svennerholm L., Biochem Biophys Acta30 124–129, 1958.Google Scholar
  21. 21.
    Jameson P. and Levine A.S., J Bacteriol90 563–564, 1965.Google Scholar
  22. 22.
    Dimmock N.J., J Gen Virol13 481–483, 1971.Google Scholar
  23. 23.
    Ward C.W., Murray J.M. Roxburgh C.M. and Jackson D.C., Virology126 370–375, 1983.Google Scholar
  24. 24.
    Griffin J.A., Basak S., and Compans R.W., Virology125 324–334, 1983.Google Scholar
  25. 25.
    Lentz M.R., Webster R.G., and Air G.M., Biochemistry26 5351–5358, 1987.Google Scholar
  26. 26.
    Li S., Schulman J., Hamura S., and Palese P., J Virol67 6667–6673, 1993.Google Scholar
  27. 27.
    Palese P., Bucher D., and Kilbourne E.D., Appl Microbiol25 195–201, 1973.Google Scholar
  28. 28.
    Scholtissek C., Vallbracht A., Flehmig B., and Rott R., Virology95 492–500, 1979.Google Scholar
  29. 29.
    Bonin J., and Scholtissek C., Arch Virol75 255–268, 1983.Google Scholar
  30. 30.
    Schlesinger R.W., Bradshaw G.L., Barbone F., Reinacher M., Rott R., and Husak P., J Virol63 1695–1703, 1989.Google Scholar
  31. 31.
    Anders E.M., Hartley C.A., and Jackson D.C., Proc Natl Acad Sci USA87 4485–4489, 1990.Google Scholar
  32. 32.
    Hartley C.A., Jackson D.C., and Anders E.M., J Virol66 4358–4363, 1992.Google Scholar
  33. 33.
    Kawaoka Y., Naeve C.W., and Webster R.G. Virology139 303–316, 1984.Google Scholar
  34. 34.
    Ward A.C. and de Koning-Ward T.F., Virus Genes,10 179–183, 1995.Google Scholar

Copyright information

© Kluwer Academic Publishers 1995

Authors and Affiliations

  1. 1.Biomolecular Research Institute and Russell Grimwade School of BiochemistryUniversity of MelbourneParkvilleAustralia

Personalised recommendations