High-throughput neuraminidase substrate specificity study of human and avian influenza A viruses

Virology. 2011 Jun 20;415(1):12-9. doi: 10.1016/j.virol.2011.03.024. Epub 2011 Apr 17.

Abstract

Despite the importance of neuraminidase (NA) activity in effective infection by influenza A viruses, limited information exists about the differences of substrate preferences of viral neuraminidases from different hosts or from different strains. Using a high-throughput screening format and a library of twenty α2-3- or α2-6-linked para-nitrophenol-tagged sialylgalactosides, substrate specificity of NAs on thirty-seven strains of human and avian influenza A viruses was studied using intact viral particles. Neuraminidases of all viruses tested cleaved both α2-3- and α2-6-linked sialosides but preferred α2-3-linked ones and the activity was dependent on the terminal sialic acid structure. In contrast to NAs of other subtypes of influenza A viruses which did not cleave 2-keto-3-deoxy-d-glycero-d-galacto-nonulosonic acid (Kdn) or 5-deoxy Kdn (5d-Kdn), NAs of all N7 subtype viruses tested had noticeable hydrolytic activities on α2-3-linked sialosides containing Kdn or 5d-Kdn. Additionally, group 1 NAs showed efficient activity in cleaving N-azidoacetylneuraminic acid from α2-3-linked sialoside.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Birds / virology
  • Carbohydrate Conformation
  • Galactosides / chemistry
  • Galactosides / metabolism*
  • High-Throughput Screening Assays
  • Humans
  • Influenza A Virus, H9N2 Subtype / enzymology
  • Influenza A virus / enzymology*
  • Influenza in Birds / virology
  • Influenza, Human / virology
  • N-Acetylneuraminic Acid / chemistry
  • N-Acetylneuraminic Acid / metabolism
  • Neuraminidase / antagonists & inhibitors
  • Neuraminidase / chemistry
  • Neuraminidase / metabolism*
  • Substrate Specificity

Substances

  • Galactosides
  • Neuraminidase
  • N-Acetylneuraminic Acid