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Comprehensive analysis of N-glycans in IgG purified from ferrets with or without influenza A virus infection.


ABSTRACT: Influenza viruses cause contagious respiratory infections, resulting in significant economic burdens to communities. Production of influenza-specific Igs, specifically IgGs, is one of the major protective immune mechanisms against influenza viruses. In humans, N-glycosylation of IgGs plays a critical role in antigen binding and effector functions. The ferret is the most commonly used animal model for studying influenza pathogenesis, virus transmission, and vaccine development, but its IgG structure and functions remain largely undefined. Here we show that ferret IgGs are N-glycosylated and that their N-glycan structures are diverse. Using a comprehensive strategy based on MS and ultra-HPLC analyses in combination with exoglycosidase digestions, we assigned 42 N-glycan structures in ferret IgGs. We observed that N-glycans of ferret IgGs consist mainly of complex-type glycans, including some high-mannose and hybrid glycans, similar to those observed in human IgG. The complex-type glycans of ferret IgGs were primarily core-fucosylated. Furthermore, a fraction of N-glycans carried bisecting GlcNAc. Ferret IgGs also had a minor fraction of glycans carrying ?2-6Neu5Ac(s). We noted that, unlike human IgG, ferret IgGs have ?Gal epitopes on some N-glycans. Interestingly, influenza A infection caused prominent changes in the N-glycans of ferret IgG, mainly because of an increase in bisecting GlcNAc and F1A2G0 and a corresponding decrease in F1A2G1. This suggests that the glycosylation of virus-specific IgG may play a role in its functionality. Our study highlights the need to further elucidate the structure-function relationships of IgGs in universal influenza vaccine development.

SUBMITTER: Zou G 

PROVIDER: S-EPMC6302183 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Comprehensive analysis of <i>N</i>-glycans in IgG purified from ferrets with or without influenza A virus infection.

Zou Guozhang G   Kosikova Martina M   Kim Su-Ryun SR   Kotian Shweta S   Wu Wells W WW   Shen Rongfong R   Powers David N DN   Agarabi Cyrus C   Xie Hang H   Ju Tongzhong T  

The Journal of biological chemistry 20181012 50


Influenza viruses cause contagious respiratory infections, resulting in significant economic burdens to communities. Production of influenza-specific Igs, specifically IgGs, is one of the major protective immune mechanisms against influenza viruses. In humans, <i>N</i>-glycosylation of IgGs plays a critical role in antigen binding and effector functions. The ferret is the most commonly used animal model for studying influenza pathogenesis, virus transmission, and vaccine development, but its IgG  ...[more]

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