期刊
VIROLOGY
卷 413, 期 1, 页码 84-92出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2011.01.036
关键词
Collectin; Innate; Mice; Influenza; Virulence
类别
资金
- National Health and Medical Research Council (NHMRC) of Australia [4509230]
- Australian Government Department of Health and Ageing
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. (C) 2011 Elsevier Inc. All rights reserved.
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