title: A mutant influenza virus that uses an N1 neuraminidase as the receptor-binding protein.
abstract: In the vast majority of influenza A viruses characterized to date, hemagglutinin (HA) is the receptor-binding and fusion protein, whereas neuraminidase (NA) is a receptor-cleaving protein that facilitates viral release but is expendable for entry. However, the NAs of some recent human H3N2 isolates have acquired receptor-binding activity via the mutation D151G, although these isolates also appear to retain the ability to bind receptors via HA. We report here the laboratory generation of a mutation (G147R) that enables an N1 NA to completely co-opt the receptor-binding function normally performed by HA. Viruses with this mutant NA grow to high titers even in the presence of extensive mutations to conserved residues in HA's receptor-binding pocket. When the receptor-binding NA is paired with this binding-deficient HA, viral infectivity and red blood cell agglutination are blocked by NA inhibitors. Furthermore, virus-like particles expressing only the receptor-binding NA agglutinate red blood cells in an NA-dependent manner. Although the G147R NA receptor-binding mutant virus that we characterize is a laboratory creation, this same mutation is found in several natural clusters of H1N1 and H5N1 viruses. Our results demonstrate that, at least in tissue culture, influenza virus receptor-binding activity can be entirely shifted from HA to NA.
authors.affiliation: Molecular and Cellular Biology Program, University of Washington, Seattle, Washington, USA.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Hooper
authors.forename: Jesse D
authors.initials: JD
authors.lastname: Bloom
mesh_terms: D000818:Animals; D002460:Cell Line; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000201:enzymology / Q000235:genetics; D053122:Influenza A Virus, H3N2 Subtype / Q000201:enzymology* / Q000235:genetics; D053124:Influenza A Virus, H5N1 Subtype / Q000201:enzymology / Q000235:genetics; D009980:Influenza A virus / Q000145:classification / Q000201:enzymology / Q000235:genetics; D007251:Influenza, Human / Q000378:metabolism* / Q000821:virology; D051379:Mice; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009439:Neuraminidase / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D011485:Protein Binding; D011991:Receptors, Virus / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011991:Receptors, Virus; D014764:Viral Proteins; C487630:NA protein, influenza A virus; D009439:Neuraminidase
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