| Specific Sites of N-Linked Glycosylation on the Hemagglutinin of H1N1 Subtype Influenza A Virus Determine Sensitivity to Inhibitors of the Innate Immune System and Virulence in Mice. | |
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MedLine Citation:
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PMID: 21768397 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Oligosaccharides on the hemagglutinin (HA) and neuraminidase of influenza A virus (IAV) are a target for recognition by lectins of the innate immune system, including soluble surfactant protein-D and the macrophage mannose receptor on airway macrophages. Glycans attached to the head of H1 subtype of IAV differ markedly in number and location. A reverse genetic approach was used to define the importance of particular N-glycosylation sites on H1 in determining sensitivity to innate immune defenses and virulence in mice. The HA of A/PR/8/34 (PR8, H1N1) and A/Brazil/11/78 (Brazil, H1N1) express zero and four glycosylation sites on the head of HA, respectively. Site-directed mutagenesis was used to add (PR8) or delete (Brazil) glycosylation sites, and IAV expressing wild-type or mutant HA were generated on a PR8 backbone. Addition or removal of particular glycans modulated sensitivity to mouse lung fluids but was not a major factor determining susceptibility of airway macrophages to infection. PR8 is a mouse-adapted virus, and mutations in multiple IAV genes have been shown to contribute to virulence, yet addition of glycosylation to PR8 HA was sufficient to attenuate disease. In contrast, removal of glycans from Brazil HA resulted in severe disease and death. These studies provide insight regarding the mechanisms by which IAV can induce disease in mice. Moreover, reduced glycosylation of HA is likely to be an important factor associated with adaptation of human IAV to growth in mouse lung. |
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Authors:
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Michelle D Tate; Andrew G Brooks; Patrick C Reading |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-7-18 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: - ISSN: 1550-6606 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-7-19 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Microbiology and Immunology, University of Melbourne, Melbourne, Victoria 3010, Australia. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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