Shotgun glycomics of pig lung identifies natural endogenous receptors for influenza viruses

• Type of Material: Article
• Authors: Lauren Byrd-Leotis, Emory University; Renpeng Liu, Emory University; Konrad C. Bradley, Emory University; Yi Lasanajak, Emory University; Sandra F. Cummings, Emory University; Xuezheng Song, Emory University; Jamie Heimburg-Molinaro, Emory University; Summer Galloway, Emory University; Marie R. Culhane, University of Minnesota; David Smith, Emory University; David Steinhauer, Emory University; Richard Cummings, Emory University
• Language: English
• Date: 2014-06-03
• Publisher: National Academy of Sciences
• Publication Version: Final Published Version
• Copyright Statement: Copyright © 2020 National Academy of Sciences.
• Final Published Version (URL): http://dx.doi.org/10.1073/pnas.1323162111
• Title of Journal or Parent Work: Proceedings of the National Academy of Sciences
• ISSN: 0027-8424
• Volume: 111
• Issue: 22
• Start Page: E2241
• End Page: E2250
• Grant/Funding Information: This work was supported by the US Department of Health and Human Services Grants HHSN266200700006C and HHSN272201400006C (National Institute of Allergy and Infectious Diseases Centers of Excellence for Influenza Research and Surveillance); and National Institutes of Health Grants GM098791 (to R.D.C.) and GM085448 (to D.F.S.).
• Keywords: Science & Technology; L BARK LECTIN; O-LINKED GLYCANS; MASS-SPECTROMETRY; receptor binding; MICROARRAY STRATEGY; A VIRUSES; virus attachment; Multidisciplinary Sciences; hemagglutinin; RICINUS-COMMUNIS AGGLUTININ; GLYCAN-BINDING-PROTEINS; SIALIC-ACID; Science & Technology - Other Topics; STRUCTURAL DETERMINANTS; PANDEMIC INFLUENZA
• Research Categories: Chemistry, Biochemistry; Biology, Microbiology

Abstract

Influenza viruses bind to host cell surface glycans containing terminal sialic acids, but as studies on influenza binding become more sophisticated, it is becoming evident that although sialic acid may be necessary, it is not sufficient for productive binding. To better define endogenous glycans that serve as viral receptors, we have explored glycan recognition in the pig lung, because influenza is broadly disseminated in swine, and swine have been postulated as an intermediary host for the emergence of pandemic strains. For these studies, we used the technology of "shotgun glycomics" to identify natural receptor glycans. The total released N- and O-glycans from pig lung glycoproteins and glycolipid-derived glycans were fluorescently tagged and separated by multidimensional HPLC, and individual glycans were covalently printed to generate pig lung shotgun glycan microarrays. All viruses tested interacted with one or more sialylated N-glycans but not O-glycans or glycolipid-derived glycans, and each virus demonstrated novel and unexpected differences in endogenous N-glycan recognition. The results illustrate the repertoire of specific, endogenous N-glycans of pig lung glycoproteins for virus recognition and offer a new direction for studying endogenous glycan functions in viral pathogenesis.