Glycosylation of the hemagglutinin modulates the sensitivity of H3N2 influenza viruses to innate proteins in airway secretions and virulence in mice.
Virology
; 413(1): 84-92, 2011 Apr 25.
Article
em En
| MEDLINE
| ID: mdl-21353279
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 71 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sistema Respiratório
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Influenza Humana
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Vírus da Influenza A Subtipo H3N2
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Hemaglutininas Virais
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article