Archives of Virology

, Volume 142, Issue 1, pp 75–88

Changes in the hemagglutinin molecule of influenza type A (H3N2) virus associated with increased virulence for mice

  • C. A. Hartley
  • P. C. Reading
  • A. C. Ward
  • E. M. Anders
Article

DOI: 10.1007/s007050050060

Cite this article as:
Hartley, C.A., Reading, P.C., Ward, A.C. et al. Arch. Virol. (1997) 142: 75. doi:10.1007/s007050050060

Summary

The H3N2 influenza virus A/Philippines/82 (Phil82) and its bovine serum-resistant mutant, Phil82/BS, were used to investigate factors that influence virulence of influenza virus for mice. Phil82/BS, which lacks the high-mannose oligosaccharide at residue 165 of the hemagglutinin (HA) molecule, was found to replicate to a much higher titer in mouse lung than the parent Phil82, and had acquired lethality for mice. Further adaptation of Phil82/BS by sequential lung passage in mice yielded a strain of greater virulence, Phil82/BS/ML10, in which a change at residue 246 of HA resulted in loss of a second potential glycosylation site. Phil82 is highly sensitive to neutralization in vitro by murine serum- and lung-associated mannose-binding lectins (collectins). Characterization of the two mutant viruses indicated that resistance to murine collectins can account for the enhanced virulence of Phil82/BS but not for the further increase in virulence of Phil82/BS/ML10. Evidence is presented that residue 246 is not in fact glycosylated in Phil82/BS HA, nor presumably in the parent Phil82 virus. The HA molecule of Phil82/BS/ML10 displayed functional differences from Phil82/BS, including a change in the optimum pH of fusion and a minor change in receptor-binding specificity, which may allow improved efficiency of replication in the mouse lung.

Copyright information

© Springer-Verlag 1997

Authors and Affiliations

  • C. A. Hartley
    • 1
  • P. C. Reading
    • 1
  • A. C. Ward
    • 2
  • E. M. Anders
    • 1
  1. 1. Department of Microbiology, University of Melbourne, Parkville, Victoria, AustraliaAustralia
  2. 2. Biomolecular Research Institute, Parkville, Victoria, AustraliaAustralia

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