title: Recent H3N2 Viruses Have Evolved Specificity for Extended, Branched Human-type Receptors, Conferring Potential for Increased Avidity.
abstract: Human and avian influenza viruses recognize different sialic acid-containing receptors, referred to as human-type (NeuAcα2-6Gal) and avian-type (NeuAcα2-3Gal), respectively. This presents a species barrier for aerosol droplet transmission of avian viruses in humans and ferrets. Recent reports have suggested that current human H3N2 viruses no longer have strict specificity toward human-type receptors. Using an influenza receptor glycan microarray with extended airway glycans, we find that H3N2 viruses have in fact maintained human-type specificity, but they have evolved preference for a subset of receptors comprising branched glycans with extended poly-N-acetyl-lactosamine (poly-LacNAc) chains, a specificity shared with the 2009 pandemic H1N1 (Cal/04) hemagglutinin. Lipid-linked versions of extended sialoside receptors can restore susceptibility of sialidase-treated MDCK cells to infection by both recent (A/Victoria/361/11) and historical (A/Hong Kong/8/1968) H3N2 viruses. Remarkably, these human-type receptors with elongated branches have the potential to increase avidity by simultaneously binding to two subunits of a single hemagglutinin trimer.
authors.affiliation: Departments of Cell and Molecular Biology, Chemical Physiology, and Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Peng
authors.affiliation: Departments of Cell and Molecular Biology, Chemical Physiology, and Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: de Vries
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia, Athens, GA, USA.
authors.forename: Oliver C
authors.initials: OC
authors.lastname: Grant
authors.affiliation: Departments of Cell and Molecular Biology, Chemical Physiology, and Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Thompson
authors.affiliation: Departments of Cell and Molecular Biology, Chemical Physiology, and Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: McBride
authors.affiliation: Departments of Cell and Molecular Biology, Chemical Physiology, and Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Buyankhishig
authors.initials: B
authors.lastname: Tsogtbaatar
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Lee
authors.affiliation: Departments of Cell and Molecular Biology, Chemical Physiology, and Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Nahid
authors.initials: N
authors.lastname: Razi
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.|Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Wilson
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia, Athens, GA, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Woods
authors.affiliation: Departments of Cell and Molecular Biology, Chemical Physiology, and Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Paulson
mesh_terms: D000818:Animals; D002460:Cell Line; D004285:Dogs; D005685:Galactans / Q000378:metabolism; D057809:HEK293 Cells; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000378:metabolism*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000378:metabolism; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics / Q000378:metabolism*; D053123:Influenza A Virus, H3N8 Subtype / Q000378:metabolism; D053124:Influenza A Virus, H5N1 Subtype / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D056004:Molecular Dynamics Simulation; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism*; D013045:Species Specificity; D053585:Virus Attachment
chemical_list: D005685:Galactans; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011134:Polysaccharides; D011991:Receptors, Virus; C023041:poly-N-acetylgalactosamine; D019158:N-Acetylneuraminic Acid
keywords: H3N2; airway; bidentate binding; chemo-enzymatic synthesis; extended branched glycans; hemagglutinin; influenza virus; poly-N-acetyl-lactosamine; receptor specificity; sialoside microarray