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

• Authors: Nan Jia, Harvard Medical School; Lauren Byrd-Leotis, Harvard Medical School; Yasuyuki Matsumoto, Harvard Medical School; Chao Gao, Harvard Medical School; Alexander N. Wein, Emory University; Jenna L. Lobby, Emory University; Jacob Kohlmeier, Emory University; David Steinhauer, Emory University; Richard Cummings, Emory University
• Journal Title: Scientific Reports
• Volume: Volume 10, Number 1
• Publisher: Nature Research (part of Springer Nature): Fully open access journals | 2020-12-01, Pages 5320-5320
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1038/s41598-020-62074-z
• Subjects: Biology, Microbiology; Health Sciences, Immunology
• Keywords: Glycoconjugates; Glycobiology; Influenza virus

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.