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Glycosylation focuses sequence variation in the influenza A virus H1 hemagglutinin globular domain.

Das SR, Puigbò P, Hensley SE, Hurt DE, Bennink JR, Yewdell JW - PLoS Pathog. (2010)

Bottom Line: The FI predicts the predominance of glycosylation states among existing strains.Our analyses show that while the number of glycosylation sites in the HA globular domain does not influence the overall magnitude of variation in defined antigenic regions, variation focuses on those regions unshielded by glycosylation.This supports the conclusion that glycosylation generally shields HA from antibody-mediated neutralization, and implies that fitness costs in accommodating oligosaccharides limit virus escape via HA hyperglycosylation.

View Article: PubMed Central - PubMed

Affiliation: NIAID, Bethesda, MA, USA.

ABSTRACT
Antigenic drift in the influenza A virus hemagglutinin (HA) is responsible for seasonal reformulation of influenza vaccines. Here, we address an important and largely overlooked issue in antigenic drift: how does the number and location of glycosylation sites affect HA evolution in man? We analyzed the glycosylation status of all full-length H1 subtype HA sequences available in the NCBI influenza database. We devised the "flow index" (FI), a simple algorithm that calculates the tendency for viruses to gain or lose consensus glycosylation sites. The FI predicts the predominance of glycosylation states among existing strains. Our analyses show that while the number of glycosylation sites in the HA globular domain does not influence the overall magnitude of variation in defined antigenic regions, variation focuses on those regions unshielded by glycosylation. This supports the conclusion that glycosylation generally shields HA from antibody-mediated neutralization, and implies that fitness costs in accommodating oligosaccharides limit virus escape via HA hyperglycosylation.

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Distribution of glycosylation sites H3N2 viruses.H3N2 viruses were binned according to the number of glycosylation sites in the globular domain as indicated. Plotted is the percentage of viruses with glycosylation sites in the position designated. A total of 2791 H3N2 full-length sequences were used in this analysis.
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ppat-1001211-g006: Distribution of glycosylation sites H3N2 viruses.H3N2 viruses were binned according to the number of glycosylation sites in the globular domain as indicated. Plotted is the percentage of viruses with glycosylation sites in the position designated. A total of 2791 H3N2 full-length sequences were used in this analysis.

Mentions: H3N2 viruses have up to six glycosylation sites on the globular domain of HA (Figure 6). When we sorted H3 sequences based on number of glycosylation sites, we found a distinct trend compared to H1 HA in acquiring glycosylation sites. Position 168 is the most conserved position glycosylation in H3 sequences. When there is one glycosylation, it's nearly invariably at position 168 (with a few isolates with lone glycosylation at position 84). Double glycosylation is dominated by the 84, 168 pairing. Remarkably, triple gycosylation is dominated by 168 with two novel sites: 66 and 129. Adding glycosylation at residue 259 uniformly attains four-site glycosylation. Adding sites between residues 129 and 168 achieve higher order glycosylation.


Glycosylation focuses sequence variation in the influenza A virus H1 hemagglutinin globular domain.

Das SR, Puigbò P, Hensley SE, Hurt DE, Bennink JR, Yewdell JW - PLoS Pathog. (2010)

Distribution of glycosylation sites H3N2 viruses.H3N2 viruses were binned according to the number of glycosylation sites in the globular domain as indicated. Plotted is the percentage of viruses with glycosylation sites in the position designated. A total of 2791 H3N2 full-length sequences were used in this analysis.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2991263&req=5

ppat-1001211-g006: Distribution of glycosylation sites H3N2 viruses.H3N2 viruses were binned according to the number of glycosylation sites in the globular domain as indicated. Plotted is the percentage of viruses with glycosylation sites in the position designated. A total of 2791 H3N2 full-length sequences were used in this analysis.
Mentions: H3N2 viruses have up to six glycosylation sites on the globular domain of HA (Figure 6). When we sorted H3 sequences based on number of glycosylation sites, we found a distinct trend compared to H1 HA in acquiring glycosylation sites. Position 168 is the most conserved position glycosylation in H3 sequences. When there is one glycosylation, it's nearly invariably at position 168 (with a few isolates with lone glycosylation at position 84). Double glycosylation is dominated by the 84, 168 pairing. Remarkably, triple gycosylation is dominated by 168 with two novel sites: 66 and 129. Adding glycosylation at residue 259 uniformly attains four-site glycosylation. Adding sites between residues 129 and 168 achieve higher order glycosylation.

Bottom Line: The FI predicts the predominance of glycosylation states among existing strains.Our analyses show that while the number of glycosylation sites in the HA globular domain does not influence the overall magnitude of variation in defined antigenic regions, variation focuses on those regions unshielded by glycosylation.This supports the conclusion that glycosylation generally shields HA from antibody-mediated neutralization, and implies that fitness costs in accommodating oligosaccharides limit virus escape via HA hyperglycosylation.

View Article: PubMed Central - PubMed

Affiliation: NIAID, Bethesda, MA, USA.

ABSTRACT
Antigenic drift in the influenza A virus hemagglutinin (HA) is responsible for seasonal reformulation of influenza vaccines. Here, we address an important and largely overlooked issue in antigenic drift: how does the number and location of glycosylation sites affect HA evolution in man? We analyzed the glycosylation status of all full-length H1 subtype HA sequences available in the NCBI influenza database. We devised the "flow index" (FI), a simple algorithm that calculates the tendency for viruses to gain or lose consensus glycosylation sites. The FI predicts the predominance of glycosylation states among existing strains. Our analyses show that while the number of glycosylation sites in the HA globular domain does not influence the overall magnitude of variation in defined antigenic regions, variation focuses on those regions unshielded by glycosylation. This supports the conclusion that glycosylation generally shields HA from antibody-mediated neutralization, and implies that fitness costs in accommodating oligosaccharides limit virus escape via HA hyperglycosylation.

Show MeSH
Related in: MedlinePlus