Limits...
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.

Show MeSH

Related in: MedlinePlus

Relationship between amino acid variability and presence of glycosylation sites in Swine H1 globular domain.The plots correspond to a) Swine-origin 2009 H1N1 HA sequences (31st March, 2010) which has 1 glycosylation site in region 91; b) Swine-origin 2009 H1N1 HA sequences (12th October, 2009) which has 1 glycosylation site in region 91; c) Human virus HAs from 1918–2008 with 1 glycosylation site in region 91; d) Swine virus HA sequences from 1918–2008 with 1 glycosylation site in region 91. The positions and the number of possible amino acids of hyper-variable regions are shown as in Figure 3.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2991263&req=5

ppat-1001211-g009: Relationship between amino acid variability and presence of glycosylation sites in Swine H1 globular domain.The plots correspond to a) Swine-origin 2009 H1N1 HA sequences (31st March, 2010) which has 1 glycosylation site in region 91; b) Swine-origin 2009 H1N1 HA sequences (12th October, 2009) which has 1 glycosylation site in region 91; c) Human virus HAs from 1918–2008 with 1 glycosylation site in region 91; d) Swine virus HA sequences from 1918–2008 with 1 glycosylation site in region 91. The positions and the number of possible amino acids of hyper-variable regions are shown as in Figure 3.

Mentions: As seen in Figure 9, despite their limited time in humans, SOIVs demonstrate a remarkable amount of variation, peaking around positions 225 and 264, with other hot spots at residues 77 and 135 (Figure 9b). This pattern differs from human H1N1 isolated from 1918 to present (Figure 9c), which show far less variation at residues 225 and 264 regions while focusing variation near 77, 135 and 190 regions. Classic swine viruses (Figure 9d) show a different pattern of variation, focused at residues 147 and 200 (note that the data shown in Figure 3b include all isolates with a single glycosylation site at position 91).


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 Swine H1 globular domain.The plots correspond to a) Swine-origin 2009 H1N1 HA sequences (31st March, 2010) which has 1 glycosylation site in region 91; b) Swine-origin 2009 H1N1 HA sequences (12th October, 2009) which has 1 glycosylation site in region 91; c) Human virus HAs from 1918–2008 with 1 glycosylation site in region 91; d) Swine virus HA sequences from 1918–2008 with 1 glycosylation site in region 91. The positions and the number of possible amino acids of hyper-variable regions are shown as in Figure 3.
© Copyright Policy
Related In: Results  -  Collection

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

ppat-1001211-g009: Relationship between amino acid variability and presence of glycosylation sites in Swine H1 globular domain.The plots correspond to a) Swine-origin 2009 H1N1 HA sequences (31st March, 2010) which has 1 glycosylation site in region 91; b) Swine-origin 2009 H1N1 HA sequences (12th October, 2009) which has 1 glycosylation site in region 91; c) Human virus HAs from 1918–2008 with 1 glycosylation site in region 91; d) Swine virus HA sequences from 1918–2008 with 1 glycosylation site in region 91. The positions and the number of possible amino acids of hyper-variable regions are shown as in Figure 3.
Mentions: As seen in Figure 9, despite their limited time in humans, SOIVs demonstrate a remarkable amount of variation, peaking around positions 225 and 264, with other hot spots at residues 77 and 135 (Figure 9b). This pattern differs from human H1N1 isolated from 1918 to present (Figure 9c), which show far less variation at residues 225 and 264 regions while focusing variation near 77, 135 and 190 regions. Classic swine viruses (Figure 9d) show a different pattern of variation, focused at residues 147 and 200 (note that the data shown in Figure 3b include all isolates with a single glycosylation site at position 91).

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