title: Glycosylation of the hemagglutinin modulates the sensitivity of H3N2 influenza viruses to innate proteins in airway secretions and virulence in mice.
abstract: Collectins in airway fluids and membrane-associated lectins such as the macrophage mannose receptor (MMR) recognize mannose-rich glycans on the envelope glycoproteins of influenza A viruses. In this study, we used a reverse genetic approach to examine the role of particular N-linked glycosylation sites on the hemagglutinin (HA) of A/Beijing/353/89 (Beij/89, H3N2) in determining sensitivity to lectin-mediated immune defenses and virulence in mice. We generated 7:1 reassortant viruses on an A/PR/8/34 'backbone' with Beij/89 HA or HA lacking one or more glycosylation sites. Asn(165) was an important determinant of sensitivity to mouse collectins and virulence but did not alter susceptibility of airway macrophages to infection. Removal of both Asn(165) and Asn(246) led to a further increase in virulence, characterized by enhanced virus replication, pulmonary inflammation and vascular leak. These studies define the importance of particular glycans on H3 HA in determining sensitivity to airway collectins and virulence in mice.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Victoria 3010, Australia.
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Tate
authors.forename: Emma R
authors.initials: ER
authors.lastname: Job
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Brooks
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Reading
mesh_terms: D000818:Animals; D037222:Collectins / Q000235:genetics / Q000276:immunology; D006031:Glycosylation; D006389:Hemagglutinins, Viral / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012137:Respiratory System / Q000276:immunology* / Q000821:virology; D014774:Virulence
chemical_list: D037222:Collectins; D006389:Hemagglutinins, Viral