title: Identification of critical residues of influenza neuraminidase in viral particle release.
abstract: BACKGROUND
  Influenza neuraminidase (NA) is essential for virus release from its host cells and it is one of the targets for structure-based antiviral drug design.
  
  
  RESULTS
  In this report, we established a pseudoviral particle release assay to study NA function, which is based on lentiviral particles pseudotyped with influenza glycoproteins HA and NA as a surrogate system. Through an extensive molecular analysis, we sought to characterize important residues governing NA function. We identified five residues of NA, 234, 241, 257, 286 and 345, four of which (except 345) map away from the active site of NA when projected onto the three-dimensional structure of avian influenza H5N1 NA, and substitutions of these residues adversely affected the NA-mediated viral particle release, suggesting that these residues are critical for NA enzymatic activity.
  
  
  CONCLUSIONS
  Through extensive chimeric and mutational analyses, we have identified several residues, which map away from the active site and are critical for NA function. These findings provide new insights into NA-mediated pseudoviral particle release and may have important implications in drug design and therapeutics against influenza infection.
authors.affiliation: Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Tisoncik
authors.forename: Ying
authors.initials: Y
authors.lastname: Guo
authors.forename: Katie S
authors.initials: KS
authors.lastname: Cordero
authors.forename: Jia
authors.initials: J
authors.lastname: Yu
authors.forename: Jianwei
authors.initials: J
authors.lastname: Wang
authors.forename: Youjia
authors.initials: Y
authors.lastname: Cao
authors.forename: Lijun
authors.initials: L
authors.lastname: Rong
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D004252:DNA Mutational Analysis; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000502:physiology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D020125:Mutation, Missense; D009439:Neuraminidase / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D016415:Sequence Alignment; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D057074:Virus Release
chemical_list: D050505:Mutant Proteins; D014764:Viral Proteins; C487630:NA protein, influenza A virus; D009439:Neuraminidase