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Loss of a single N-linked glycan from the hemagglutinin of influenza virus is associated with resistance to collectins and increased virulence in mice

BACKGROUND: Glycosylation on the globular head of the hemagglutinin (HA) protein of influenza virus acts as an important target for recognition and destruction of virus by innate immune proteins of the collectin family. This, in turn, modulates the virulence of different viruses for mice. The role o...

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Autores principales: Reading, Patrick C, Pickett, Danielle L, Tate, Michelle D, Whitney, Paul G, Job, Emma R, Brooks, Andrew G
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2787511/
https://www.ncbi.nlm.nih.gov/pubmed/19930664
http://dx.doi.org/10.1186/1465-9921-10-117
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author Reading, Patrick C
Pickett, Danielle L
Tate, Michelle D
Whitney, Paul G
Job, Emma R
Brooks, Andrew G
author_facet Reading, Patrick C
Pickett, Danielle L
Tate, Michelle D
Whitney, Paul G
Job, Emma R
Brooks, Andrew G
author_sort Reading, Patrick C
collection PubMed
description BACKGROUND: Glycosylation on the globular head of the hemagglutinin (HA) protein of influenza virus acts as an important target for recognition and destruction of virus by innate immune proteins of the collectin family. This, in turn, modulates the virulence of different viruses for mice. The role of particular oligosaccharide attachments on the HA in determining sensitivity to collectins has yet to be fully elucidated. METHODS: When comparing the virulence of H3N2 subtype viruses for mice we found that viruses isolated after 1980 were highly glycosylated and induced mild disease in mice. During these studies, we were surprised to find a small plaque variant of strain A/Beijing/353/89 (Beij/89) emerged following infection of mice and grew to high titres in mouse lung. In the current study we have characterized the properties of this small plaque mutant both in vitro and in vivo. RESULTS: Small plaque mutants were recovered following plaquing of lung homogenates from mice infected with influenza virus seed Beij/89. Compared to wild-type virus, small plaque mutants showed increased virulence in mice yet did not differ in their ability to infect or replicate in airway epithelial cells in vitro. Instead, small plaque variants were markedly resistant to neutralization by murine collectins, a property that correlated with the acquisition of an amino acid substitution at residue 246 on the viral HA. We present evidence that this substitution was associated with the loss of an oligosaccharide glycan from the globular head of HA. CONCLUSION: A point mutation in the gene encoding the HA of Beij/89 was shown to ablate a glycan attachment site. This was associated with resistance to collectins and increased virulence in mice.
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spelling pubmed-27875112009-12-03 Loss of a single N-linked glycan from the hemagglutinin of influenza virus is associated with resistance to collectins and increased virulence in mice Reading, Patrick C Pickett, Danielle L Tate, Michelle D Whitney, Paul G Job, Emma R Brooks, Andrew G Respir Res Research BACKGROUND: Glycosylation on the globular head of the hemagglutinin (HA) protein of influenza virus acts as an important target for recognition and destruction of virus by innate immune proteins of the collectin family. This, in turn, modulates the virulence of different viruses for mice. The role of particular oligosaccharide attachments on the HA in determining sensitivity to collectins has yet to be fully elucidated. METHODS: When comparing the virulence of H3N2 subtype viruses for mice we found that viruses isolated after 1980 were highly glycosylated and induced mild disease in mice. During these studies, we were surprised to find a small plaque variant of strain A/Beijing/353/89 (Beij/89) emerged following infection of mice and grew to high titres in mouse lung. In the current study we have characterized the properties of this small plaque mutant both in vitro and in vivo. RESULTS: Small plaque mutants were recovered following plaquing of lung homogenates from mice infected with influenza virus seed Beij/89. Compared to wild-type virus, small plaque mutants showed increased virulence in mice yet did not differ in their ability to infect or replicate in airway epithelial cells in vitro. Instead, small plaque variants were markedly resistant to neutralization by murine collectins, a property that correlated with the acquisition of an amino acid substitution at residue 246 on the viral HA. We present evidence that this substitution was associated with the loss of an oligosaccharide glycan from the globular head of HA. CONCLUSION: A point mutation in the gene encoding the HA of Beij/89 was shown to ablate a glycan attachment site. This was associated with resistance to collectins and increased virulence in mice. BioMed Central 2009 2009-11-23 /pmc/articles/PMC2787511/ /pubmed/19930664 http://dx.doi.org/10.1186/1465-9921-10-117 Text en Copyright ©2009 Reading et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Reading, Patrick C
Pickett, Danielle L
Tate, Michelle D
Whitney, Paul G
Job, Emma R
Brooks, Andrew G
Loss of a single N-linked glycan from the hemagglutinin of influenza virus is associated with resistance to collectins and increased virulence in mice
title Loss of a single N-linked glycan from the hemagglutinin of influenza virus is associated with resistance to collectins and increased virulence in mice
title_full Loss of a single N-linked glycan from the hemagglutinin of influenza virus is associated with resistance to collectins and increased virulence in mice
title_fullStr Loss of a single N-linked glycan from the hemagglutinin of influenza virus is associated with resistance to collectins and increased virulence in mice
title_full_unstemmed Loss of a single N-linked glycan from the hemagglutinin of influenza virus is associated with resistance to collectins and increased virulence in mice
title_short Loss of a single N-linked glycan from the hemagglutinin of influenza virus is associated with resistance to collectins and increased virulence in mice
title_sort loss of a single n-linked glycan from the hemagglutinin of influenza virus is associated with resistance to collectins and increased virulence in mice
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2787511/
https://www.ncbi.nlm.nih.gov/pubmed/19930664
http://dx.doi.org/10.1186/1465-9921-10-117
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