title: Highly Pathogenic Influenza A(H5Nx) Viruses with Altered H5 Receptor-Binding Specificity.
abstract: Emergence and intercontinental spread of highly pathogenic avian influenza A(H5Nx) virus clade 2.3.4.4 is unprecedented. H5N8 and H5N2 viruses have caused major economic losses in the poultry industry in Europe and North America, and lethal human infections with H5N6 virus have occurred in Asia. Knowledge of the evolution of receptor-binding specificity of these viruses, which might affect host range, is urgently needed. We report that emergence of these viruses is accompanied by a change in receptor-binding specificity. In contrast to ancestral clade 2.3.4 H5 proteins, novel clade 2.3.4.4 H5 proteins bind to fucosylated sialosides because of substitutions K222Q and S227R, which are unique for highly pathogenic influenza virus H5 proteins. North American clade 2.3.4.4 virus isolates have retained only the K222Q substitution but still bind fucosylated sialosides. Altered receptor-binding specificity of virus clade 2.3.4.4 H5 proteins might have contributed to emergence and spread of H5Nx viruses.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Guo
authors.forename: Erik
authors.initials: E
authors.lastname: de Vries
authors.forename: Ryan
authors.initials: R
authors.lastname: McBride
authors.forename: Jojanneke
authors.initials: J
authors.lastname: Dekkers
authors.forename: Wenjie
authors.initials: W
authors.lastname: Peng
authors.forename: Kim M
authors.initials: KM
authors.lastname: Bouwman
authors.forename: Corwin
authors.initials: C
authors.lastname: Nycholat
authors.forename: M Helene
authors.initials: MH
authors.lastname: Verheije
authors.forename: James C
authors.initials: JC
authors.lastname: Paulson
authors.forename: Frank J M
authors.initials: FJ
authors.lastname: van Kuppeveld
authors.forename: Cornelis A M
authors.initials: CA
authors.lastname: de Haan
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D000818:Animals; D004372:Ducks; D005838:Genotype; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics; D006801:Humans; D009980:Influenza A virus / Q000145:classification* / Q000302:isolation & purification / Q000472:pathogenicity / Q000502:physiology*; D005585:Influenza in Birds / Q000453:epidemiology / Q000473:pathology / Q000821:virology; D007251:Influenza, Human / Q000453:epidemiology* / Q000821:virology*; D009154:Mutation; D010802:Phylogeny; D016865:Reassortant Viruses; D011991:Receptors, Virus / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship; D056189:Viral Tropism; D053585:Virus Attachment
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011991:Receptors, Virus
keywords: H5 protein; H5Nx virus; emergence; fucosylated sialosides; hemagglutinin; highly pathogenic; influenza; influenza A virus; phylogeny; receptor binding; virus clade 2.3.4.4; viruses