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

Version 2 2024-06-03, 21:28
Version 1 2017-05-16, 15:54
journal contribution
posted on 2024-06-03, 21:28 authored by CA Hartley, PC Reading, Alister WardAlister Ward, EM Anders
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/ML 10, 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.

History

Journal

Archives of virology

Volume

142

Pagination

75-88

Location

Berlin, Germany

ISSN

0304-8608

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

1997, Springer-Verlag

Issue

1

Publisher

Springer

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