N-Glycolylneuraminic Acid as a Receptor for Influenza A Viruses

Frederik Broszeit, Netanel Tzarum, Xueyong Zhu, Nikoloz Nemanichvili, Dirk Eggink, Tim Leenders, Zeshi Li, Lin Liu, Margreet A. Wolfert, Andreas Papanikolaou, Carles Martínez-Romero, Ivan A. Gagarinov, Wenli Yu, Adolfo García-Sastre, Tom Wennekes, Masatoshi Okamatsu, Monique H. Verheije, Ian A. Wilson, Geert Jan Boons, Robert P. de Vries*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

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.

Original languageAmerican English
Pages (from-to)3284-3294.e6
JournalCell Reports
Volume27
Issue number11
DOIs
StatePublished - 11 Jun 2019
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2019 The Authors

Keywords

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

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