title: Changes in the hemagglutinin molecule of influenza type A (H3N2) virus associated with increased virulence for mice.
abstract: 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.
authors.affiliation: Department of Microbiology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: C A
authors.initials: CA
authors.lastname: Hartley
authors.forename: P C
authors.initials: PC
authors.lastname: Reading
authors.forename: A C
authors.initials: AC
authors.lastname: Ward
authors.forename: E M
authors.initials: EM
authors.lastname: Anders
mesh_terms: D000818:Animals; D002417:Cattle; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics*; D053122:Influenza A Virus, H3N2 Subtype; D009980:Influenza A virus / Q000235:genetics* / Q000472:pathogenicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D014774:Virulence / Q000235:genetics
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus