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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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Related in: MedlinePlus

Relationship between amino acid variability and presence of glycosylation sites in H3 globular domain.Variability in the globular domain of H3N2 viruses as in Figure 3. Arrows point to glycosylation sites that do not limit variability in the adjacent residues.
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ppat-1001211-g007: Relationship between amino acid variability and presence of glycosylation sites in H3 globular domain.Variability in the globular domain of H3N2 viruses as in Figure 3. Arrows point to glycosylation sites that do not limit variability in the adjacent residues.

Mentions: We next examined the correlation between the location glycosylation site and regions of variability for H3 viruses with 2 to 4 sites in the globular domain (Figure 7). Analysis of other glycoforms was compromised by either paucity of isolates in a group or by the complexity of glycosylation pattern. Although there was a reasonable correlation between the presence of a glycosylation site and absence of variation in the residues surrounding the site, this relationship was less robust than for the H1 and H2 HAs (as indicated by the arrows pointing to exceptions).


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)

Relationship between amino acid variability and presence of glycosylation sites in H3 globular domain.Variability in the globular domain of H3N2 viruses as in Figure 3. Arrows point to glycosylation sites that do not limit variability in the adjacent residues.
© Copyright Policy
Related In: Results  -  Collection

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

ppat-1001211-g007: Relationship between amino acid variability and presence of glycosylation sites in H3 globular domain.Variability in the globular domain of H3N2 viruses as in Figure 3. Arrows point to glycosylation sites that do not limit variability in the adjacent residues.
Mentions: We next examined the correlation between the location glycosylation site and regions of variability for H3 viruses with 2 to 4 sites in the globular domain (Figure 7). Analysis of other glycoforms was compromised by either paucity of isolates in a group or by the complexity of glycosylation pattern. Although there was a reasonable correlation between the presence of a glycosylation site and absence of variation in the residues surrounding the site, this relationship was less robust than for the H1 and H2 HAs (as indicated by the arrows pointing to exceptions).

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