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

PLoS Pathogens

Darrell E. Hurt¹  Suman R. Das²  Scott E. Hensley²  Jack R. Bennink²  Jonathan W. Yewdell²  Pere Puigbò³ 

[1] Computational Biology Bioinformatics and Computational Biosciences Branch (BCBB), NIAID, Bethesda, Maryland, United States of America;Laboratory of Viral Diseases, NIAID, Bethesda, Maryland, United States of America;National Center for Biotechnology Information, Bethesda, Maryland, United States of America

关键词: Glycosylation;    Viral evolution;    Influenza A virus;    Antigenic variation;    H1N1;    Protein sequencing;    Principal component analysis;    Antibodies;   

DOI  :  10.1371/journal.ppat.1001211

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY