title: Balanced hemagglutinin and neuraminidase activities are critical for efficient replication of influenza A virus.
abstract: The SD0 mutant of influenza virus A/WSN/33 (WSN), characterized by a 24-amino-acid deletion in the neuraminidase (NA) stalk, does not grow in embryonated chicken eggs because of defective NA function. Continuous passage of SD0 in eggs yielded 10 independent clones that replicated efficiently. Characterization of these egg-adapted viruses showed that five of the viruses contained insertions in the NA gene from the PB1, PB2, or NP gene, in the region linking the transmembrane and catalytic head domains, demonstrating that recombination of influenza viral RNA segments occurs relatively frequently. The other five viruses did not contain insertions in this region but displayed decreased binding affinity toward sialylglycoconjugates, compared with the binding properties of the parental virus. Sequence analysis of one of the latter viruses revealed mutations in the hemagglutinin (HA) gene, at sites in close proximity to the sialic acid receptor-binding pocket. These mutations appear to compensate for reduced NA function due to stalk deletions. Thus, balanced HA-NA functions are necessary for efficient influenza virus replication.
authors.affiliation: Department of Virology and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN 38101, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Mitnaul
authors.forename: M N
authors.initials: MN
authors.lastname: Matrosovich
authors.forename: M R
authors.initials: MR
authors.lastname: Castrucci
authors.forename: A B
authors.initials: AB
authors.lastname: Tuzikov
authors.forename: N V
authors.initials: NV
authors.lastname: Bovin
authors.forename: D
authors.initials: D
authors.lastname: Kobasa
authors.forename: Y
authors.initials: Y
authors.lastname: Kawaoka
mesh_terms: D000222:Adaptation, Physiological; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002642:Chick Embryo; D004285:Dogs; D005814:Genes, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009980:Influenza A virus / Q000235:genetics* / Q000502:physiology*; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009439:Neuraminidase / Q000235:genetics* / Q000378:metabolism; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D016601:RNA-Binding Proteins; D011956:Receptors, Cell Surface / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D014758:Viral Core Proteins / Q000235:genetics; D014771:Virion; D014779:Virus Replication / Q000235:genetics*
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D016601:RNA-Binding Proteins; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D014758:Viral Core Proteins; C092488:sialic acid receptor; D009439:Neuraminidase