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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 in H2N2 viruses and influence on HA variability.a) Distribution of glycosylation sites in H2N2 viruses as in Figure 1A, 83 full-length sequences were used in this analysis. b) Variability in the globular domain of H2N2 viruses, as in Figure 3.
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ppat-1001211-g005: Distribution of glycosylation sites in H2N2 viruses and influence on HA variability.a) Distribution of glycosylation sites in H2N2 viruses as in Figure 1A, 83 full-length sequences were used in this analysis. b) Variability in the globular domain of H2N2 viruses, as in Figure 3.

Mentions: We extended this approach to H2N2 and H3N2 HA sequences. H2N2 viruses possess a single glycosylation site in the globular domain, located at position 166 (Figure 5a). Consistent with the H1 data, analysis of H2N2 viruses showed limited variation near the sole glycosylation site at position 166 (Figure 5b).


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 in H2N2 viruses and influence on HA variability.a) Distribution of glycosylation sites in H2N2 viruses as in Figure 1A, 83 full-length sequences were used in this analysis. b) Variability in the globular domain of H2N2 viruses, as in Figure 3.
© Copyright Policy
Related In: Results  -  Collection

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

ppat-1001211-g005: Distribution of glycosylation sites in H2N2 viruses and influence on HA variability.a) Distribution of glycosylation sites in H2N2 viruses as in Figure 1A, 83 full-length sequences were used in this analysis. b) Variability in the globular domain of H2N2 viruses, as in Figure 3.
Mentions: We extended this approach to H2N2 and H3N2 HA sequences. H2N2 viruses possess a single glycosylation site in the globular domain, located at position 166 (Figure 5a). Consistent with the H1 data, analysis of H2N2 viruses showed limited variation near the sole glycosylation site at position 166 (Figure 5b).

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