title: Evolutionarily conserved residues at an oligomerization interface of the influenza A virus neuraminidase are essential for viral survival.
abstract: Neuraminidase (NA) is a homotetramer viral surface glycoprotein that is essential for virus release during influenza virus infections. Previous studies have not explored why influenza NA forms a tetramer when the bacterial monomer NA already exhibits excellent NA enzymatic activity levels. In this study, we focused on 28 highly conserved residues among all NA subtypes, identifying 21 of 28 positions as crucial residues for viral survival by using reverse genetics. Maintaining NA enzymatic activity levels is critical and numerous conserved residues were located at the oligomerization interface; however, these mutations did not affect NA enzymatic activity levels or NA cellular localization, but rather affected the stability of NA oligomerization, suggesting that the oligomerization of NA is essential for viral viability. An increased understanding of the biological functions of NA, in particular NA oligomerization, could facilitate an alternative design for antivirals to combat influenza virus infections.
authors.affiliation: Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Chee-Keng
authors.initials: CK
authors.lastname: Mok
authors.forename: Guang-Wu
authors.initials: GW
authors.lastname: Chen
authors.forename: Kuei-Chung
authors.initials: KC
authors.lastname: Shih
authors.forename: Yu-Nong
authors.initials: YN
authors.lastname: Gong
authors.forename: Sue-Jane
authors.initials: SJ
authors.lastname: Lin
authors.forename: Jim-Tong
authors.initials: JT
authors.lastname: Horng
authors.forename: John T-A
authors.initials: JT
authors.lastname: Hsu
authors.forename: Chi-Jene
authors.initials: CJ
authors.lastname: Chen
authors.forename: Shin-Ru
authors.initials: SR
authors.lastname: Shih
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000502:physiology*; D050296:Microbial Viability; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009439:Neuraminidase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011487:Protein Conformation; D055503:Protein Multimerization; D059386:Reverse Genetics; D016415:Sequence Alignment; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D014764:Viral Proteins; C487630:NA protein, influenza A virus; D009439:Neuraminidase
keywords: Conserved residues; Influenza A virus; Neuraminidase (NA); Neuraminidase (NA) enzymatic activity; Oligomerization