title: Low-pH Stability of Influenza A Virus Sialidase Contributing to Virus Replication and Pandemic.
abstract: The spike glycoprotein neuraminidase (NA) of influenza A virus (IAV) has sialidase activity that cleaves the terminal sialic acids (viral receptors) from oligosaccharide chains of glycoconjugates. A new antigenicity of viral surface glycoproteins for humans has pandemic potential. We found "low-pH stability of sialidase activity" in NA. The low-pH stability can maintain sialidase activity under acidic conditions of pH 4-5. For human IAVs, NAs of all pandemic viruses were low-pH-stable, whereas those of almost all human seasonal viruses were not. The low-pH stability was dependent on amino acid residues near the active site, the calcium ion-binding site, and the subunit interfaces of the NA homotetramer, suggesting effects of the active site and the homotetramer on structural stability. IAVs with the low-pH-stable NA showed much higher virus replication rates than those of IAVs with low-pH-unstable NA, which was correlated with maintenance of sialidase activity under an endocytic pathway of the viral cell entry mechanism, indicating contribution of low-pH stability to high replication rates of pandemic viruses. The low-pH-stable NA of the 1968 H3N2 pandemic virus was derived from the low-pH-stable NA of H2N2 human seasonal virus, one of two types classified by both low-pH stability in N2 NA and a phylogenetic tree of N2 NA genes. The 2009 H1N1 pandemic virus acquired low-pH-stable NA by two amino acid substitutions at the early stage of the 2009 pandemic. It is thought that low-pH stability contributes to infection spread in a pandemic through enhancement of virus replication.
authors.affiliation: Department of Biochemistry, School of Pharmaceutical Sciences,  University of Shizuoka.
authors.forename: Tadanobu
authors.initials: T
authors.lastname: Takahashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D019943:Amino Acid Substitution; D006801:Humans; D009980:Influenza A virus / Q000201:enzymology* / Q000472:pathogenicity; D007251:Influenza, Human / Q000453:epidemiology / Q000821:virology*; D009439:Neuraminidase / Q000737:chemistry / Q000235:genetics; D058873:Pandemics; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics; D014779:Virus Replication
chemical_list: D014764:Viral Proteins; D009439:Neuraminidase