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

• Published in: Scientific reports Vol. 10; no. 1; p. 5320
• Main Authors: Jia, Nan, Byrd-Leotis, Lauren, Matsumoto, Yasuyuki, Gao, Chao, Wein, Alexander N., Lobby, Jenna L., Kohlmeier, Jacob E., Steinhauer, David A., Cummings, Richard D.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.03.2020; Nature Publishing Group
• Subjects: 13/51; 631/326/596/1578; 631/45/221; 631/45/72/1202; 82; 82/29; Binding sites; Binding Sites - physiology; Humanities and Social Sciences; Humans; Influenza; Influenza A; Influenza A virus - metabolism; Influenza A virus - pathogenicity; Influenza, Human - metabolism; Influenza, Human - virology; Lectins; Lectins - metabolism; Ligands; Lung - metabolism; Lung - pathology; Lungs; multidisciplinary; N-Acetyllactosamine; N-glycans; Neuraminidase - pharmacology; Pathogens; Phosphorylation; Poly-N-acetyllactosamine; Polysaccharides; Polysaccharides - chemistry; Polysaccharides - metabolism; Science; Science (multidisciplinary); Sialic acids; Sialic Acids - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-62074-z

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.