Glycosylation Focuses Sequence Variation in the Influenza A Virus H1 Hemagglutinin Globular Domain

Autor: Jack R. Bennink, Pere Puigbò, Suman R. Das, Scott E. Hensley, Darrell E. Hurt, Jonathan W. Yewdell
Jazyk: angličtina
Rok vydání: 2010
Předmět:
lcsh:Immunologic diseases. Allergy
Glycosylation
animal structures
Protein Conformation
Immunology
Hemagglutinin (influenza)
Oligosaccharides
Hemagglutinin Glycoproteins
Influenza Virus
macromolecular substances
Virology/Immune Evasion
medicine.disease_cause
Microbiology
Virus
Antigenic drift
Evolution
Molecular
chemistry.chemical_compound
Protein structure
Virology
Infectious Diseases/Viral Infections
Influenza
Human
Genetics
Antigenic variation
Influenza A virus
medicine
Humans
lcsh:QH301-705.5
Molecular Biology
Antigens
Viral
biology
Computational Biology
Genetic Variation
Antigenic Variation
Computational Biology/Evolutionary Modeling
Virology/Virus Evolution and Symbiosis
carbohydrates (lipids)
Hemagglutinins
lcsh:Biology (General)
chemistry
Evolutionary Biology/Microbial Evolution and Genomics
Viral evolution
biology.protein
Parasitology
lipids (amino acids
peptides
and proteins)
lcsh:RC581-607
Research Article
Zdroj: PLoS Pathogens
PLoS Pathogens, Vol 6, Iss 11, p e1001211 (2010)
ISSN: 1553-7374
1553-7366
Popis: 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.
Author Summary Influenza A virus is highly susceptible to neutralizing antibodies specific for the viral hemagglutinin glycoprotein (HA), and is easily controlled by standard vaccines. Influenza A virus remains an important human pathogen, however, due to its ability to rapidly evade antibody responses. This process, termed antigenic drift, is due to the accumulation of amino acid substitutions that modify HA antigenic sites recognized by neutralizing antibodies. In this study, we perform bioinformatic analysis on thousands of influenza A virus isolates to better understand the influence of N-linked glycosylation on antigenic drift. HA from human IAV isolates can accommodate up to 6 oligosaccharides in its globular domain. We show that for H1, H2, and to a somewhat less extent H3, HAs, the number of glycosylation sites in the globular domain does not greatly modify the total degree of variation in antigenic sites, but rather focuses variation on sites whose access to antibodies is unaffected by glycosylation. Our findings imply that glycosylation protects HA from antibody neutralization, but functional impairment limits the number of oligosaccharides that HA can accommodate.
Databáze: OpenAIRE
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