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Cell Rep. 2019 Jun 11;27(11):3284-3294.e6. doi: 10.1016/j.celrep.2019.05.048.

N-Glycolylneuraminic Acid as a Receptor for Influenza A Viruses.

Author information

1
Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, the Netherlands.
2
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
3
Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, the Netherlands.
4
Department of Experimental Virology, Amsterdam Medical Centre, Amsterdam, the Netherlands.
5
Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA.
6
Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, the Netherlands; Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA.
7
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
8
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
9
Laboratory of Microbiology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
10
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
11
Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, the Netherlands. Electronic address: r.vries@uu.nl.

Abstract

A species barrier for the influenza A virus is the differential expression of sialic acid, which can either be α2,3-linked for avians or α2,6-linked for human viruses. The influenza A virus hosts also express other species-specific sialic acid derivatives. One major modification at C-5 is N-glycolyl (NeuGc), instead of N-acetyl (NeuAc). N-glycolyl is mammalian specific and expressed in pigs and horses, but not in humans, ferrets, seals, or dogs. Hemagglutinin (HA) adaptation to either N-acetyl or N-glycolyl is analyzed on a sialoside microarray containing both α2,3- and α2,6-linkage modifications on biologically relevant N-glycans. Binding studies reveal that avian, human, and equine HAs bind either N-glycolyl or N-acetyl. Structural data on N-glycolyl binding HA proteins of both H5 and H7 origin describe this specificity. Neuraminidases can cleave N-glycolyl efficiently, and tissue-binding studies reveal strict species specificity. The exclusive manner in which influenza A viruses differentiate between N-glycolyl and N-acetyl is indicative of selection.

KEYWORDS:

crystal structure; glycan-array; hemagglutinin; influenza A virus; neuraminidase; receptor-binding; sialic acid

PMID:
31189111
DOI:
10.1016/j.celrep.2019.05.048
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