Recent H3N2 Viruses Have Evolved Specificity for Extended, Branched Human-type Receptors, Conferring Potential for Increased Avidity

Wenjie Peng, Robert P de Vries, Oliver C Grant, Andrew J Thompson, Ryan McBride, Buyankhishig Tsogtbaatar, Peter S Lee, Nahid Razi, Ian A Wilson, Robert J Woods, James C Paulson

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Human and avian influenza viruses recognize different sialic acid-containing receptors, referred to as human-type (NeuAcα2-6Gal) and avian-type (NeuAcα2-3Gal), respectively. This presents a species barrier for aerosol droplet transmission of avian viruses in humans and ferrets. Recent reports have suggested that current human H3N2 viruses no longer have strict specificity toward human-type receptors. Using an influenza receptor glycan microarray with extended airway glycans, we find that H3N2 viruses have in fact maintained human-type specificity, but they have evolved preference for a subset of receptors comprising branched glycans with extended poly-N-acetyl-lactosamine (poly-LacNAc) chains, a specificity shared with the 2009 pandemic H1N1 (Cal/04) hemagglutinin. Lipid-linked versions of extended sialoside receptors can restore susceptibility of sialidase-treated MDCK cells to infection by both recent (A/Victoria/361/11) and historical (A/Hong Kong/8/1968) H3N2 viruses. Remarkably, these human-type receptors with elongated branches have the potential to increase avidity by simultaneously binding to two subunits of a single hemagglutinin trimer.

Original languageEnglish
Pages (from-to)23-34
Number of pages12
JournalCell Host and Microbe
Volume21
Issue number1
DOIs
Publication statusPublished - 11 Jan 2017

Keywords

  • influenza virus
  • H3N2
  • hemagglutinin
  • receptor specificity
  • airway
  • chemo-enzymatic synthesis
  • sialoside microarray
  • extended branched glycans
  • poly-N-acetyl-lactosamine
  • bidentate binding

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