1. Glycan remodeled erythrocytes facilitate antigenic characterization of recent A/H3N2 influenza viruses.
- Author
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Broszeit F, van Beek RJ, Unione L, Bestebroer TM, Chapla D, Yang JY, Moremen KW, Herfst S, Fouchier RAM, de Vries RP, and Boons GJ
- Subjects
- Antigens, Viral chemistry, Antigens, Viral genetics, Antigens, Viral metabolism, Binding Sites, Carbohydrate Sequence, Erythrocytes metabolism, Glycomics methods, Glycosides metabolism, Hemagglutination Inhibition Tests, Hemagglutinins, Viral genetics, Hemagglutinins, Viral metabolism, Host-Pathogen Interactions genetics, Humans, Influenza A Virus, H3N2 Subtype metabolism, Influenza, Human virology, Microarray Analysis methods, Polysaccharides metabolism, Protein Binding, Protein Conformation, alpha-Helical, Protein Conformation, beta-Strand, Protein Interaction Domains and Motifs, Receptors, Virus genetics, Receptors, Virus metabolism, Sialic Acids chemistry, Sialic Acids metabolism, Erythrocytes virology, Glycosides chemistry, Hemagglutinins, Viral chemistry, Influenza A Virus, H3N2 Subtype genetics, Polysaccharides chemistry, Receptors, Virus chemistry
- Abstract
During circulation in humans and natural selection to escape antibody recognition for decades, A/H3N2 influenza viruses emerged with altered receptor specificities. These viruses lost the ability to agglutinate erythrocytes critical for antigenic characterization and give low yields and acquire adaptive mutations when cultured in eggs and cells, contributing to recent vaccine challenges. Examination of receptor specificities of A/H3N2 viruses reveals that recent viruses compensated for decreased binding of the prototypic human receptor by recognizing α2,6-sialosides on extended LacNAc moieties. Erythrocyte glycomics shows an absence of extended glycans providing a rationale for lack of agglutination by recent A/H3N2 viruses. A glycan remodeling approach installing functional receptors on erythrocytes, allows antigenic characterization of recent A/H3N2 viruses confirming the cocirculation of antigenically different viruses in humans. Computational analysis of HAs in complex with sialosides having extended LacNAc moieties reveals that mutations distal to the RBD reoriented the Y159 side chain resulting in an extended receptor binding site., (© 2021. The Author(s).)
- Published
- 2021
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