NKp46 O-glycan sequences that are involved in the interaction with hemagglutinin type 1 of influenza virus

Michal Mendelson, Yoram Tekoah, Alon Zilka, Orly Gershoni-Yahalom, Roi Gazit, Hagit Achdout, Nicolai V. Bovin, Tal Meningher, Michal Mandelboim, Ofer Mandelboim, Ayelet David, Angel Porgador

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Natural killer (NK) cells serve as a crucial first-line defense against tumors and virus-infected cells. We previously showed that lysis of influenza virus (IV)-infected cells is mediated by the interaction between the NK receptor, NKp46, and the IV hemagglutinin (HA) type 1 expressed by the infected cells. This interaction requires the presence of sialyl groups on the NKp46-T225 O-glycoforms. In the current study, we analyzed the O-glycan sequences that are imperative for the interaction between recombinant NKp46 (rNKp46) and IV H1N1 strains. We first showed that rNKp46 binding to IV H1N1 is not mediated by a glycoform unique to the Thr225 site. We then characterized the O-glycan sequences that mediate the interaction of rNKp46 and IV H1N1; we employed rNKp46s with dissimilar glycosylation patterns and IV H1N1 strains with different sialic acid α2,3 and α2,6 linkage preferences. The branched α2,3-sialylated O-glycoform Neu5NAcα2,3-Galp1,4- GlcNAcβ1,6[Neu5NAcα2,3-Galβ1,3]GalNAc competently mediated the interaction of rNKp46 with IV H1N1, manifesting a preference for α2,3 linkage. In contrast, the linear α2,3-sialylated O-glycoform Neu5NAcα2,3-Galβ1,3-GalNAc was not correlated with enhanced interaction between rNKp46 and IV H1N1 or a preference for α2,3 linkage. The branched α2,3-and α2,6-sialylated O-glycoform Neu5NAcα2,3-Galp1,3[Neu5NAcα2,6]GalNAc competently mediated the interaction of rNKp46 with IV H1N1, manifesting a preference for α2,6 linkage. Previous viral HA-binding-specificity studies were performed with glycopolymer conjugates, free synthetic sialyl oligosaccharides, and sialidase-treated cells. This study shed light on the O-glycan sequences involved in the interaction of glycoprotein and viral hemagglutinins and may help in the design of agents inhibitory to hemagglutinin for influenza treatment.

Original languageEnglish
Pages (from-to)3789-3797
Number of pages9
JournalJournal of Virology
Volume84
Issue number8
DOIs
StatePublished - 1 Apr 2010

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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