The Human Lung Glycome Reveals Novel Glycan Ligands for Influenza A Virus

Sci Rep. 2020 Mar 24;10(1):5320. doi: 10.1038/s41598-020-62074-z.

Abstract

Glycans within human lungs are recognized by many pathogens such as influenza A virus (IAV), yet little is known about their structures. Here we present the first analysis of the N- and O- and glycosphingolipid-glycans from total human lungs, along with histological analyses of IAV binding. The N-glycome of human lung contains extremely large complex-type N-glycans with linear poly-N-acetyllactosamine (PL) [-3Galβ1-4GlcNAcβ1-]n extensions, which are predominantly terminated in α2,3-linked sialic acid. By contrast, smaller N-glycans lack PL and are enriched in α2,6-linked sialic acids. In addition, we observed large glycosphingolipid (GSL)-glycans, which also consists of linear PL, terminating in mainly α2,3-linked sialic acid. Histological staining revealed that IAV binds to sialylated and non-sialylated glycans and binding is not concordant with respect to binding by sialic acid-specific lectins. These results extend our understanding of the types of glycans that may serve as binding sites for human lung pathogens.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Binding Sites / physiology
  • Humans
  • Influenza A virus / metabolism
  • Influenza A virus / pathogenicity
  • Influenza, Human / metabolism*
  • Influenza, Human / virology
  • Lectins / metabolism
  • Ligands
  • Lung / metabolism*
  • Lung / pathology
  • Neuraminidase / pharmacology
  • Phosphorylation
  • Polysaccharides / chemistry*
  • Polysaccharides / metabolism
  • Sialic Acids / metabolism

Substances

  • Lectins
  • Ligands
  • Polysaccharides
  • Sialic Acids
  • Neuraminidase