title: High-throughput neuraminidase substrate specificity study of human and avian influenza A viruses.
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.
authors.affiliation: Department of Chemistry, University of California, Davis, CA 95616, USA.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Li
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Cao
authors.forename: Nguyet
authors.initials: N
authors.lastname: Dao
authors.forename: Zheng
authors.initials: Z
authors.lastname: Luo
authors.forename: Hai
authors.initials: H
authors.lastname: Yu
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xing
authors.forename: Nicole
authors.initials: N
authors.lastname: Baumgarth
authors.forename: Carol
authors.initials: C
authors.lastname: Cardona
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D001717:Birds / Q000821:virology; D002236:Carbohydrate Conformation; D005697:Galactosides / Q000737:chemistry / Q000378:metabolism*; D057166:High-Throughput Screening Assays; D006801:Humans; D053127:Influenza A Virus, H9N2 Subtype / Q000201:enzymology; D009980:Influenza A virus / Q000201:enzymology*; D005585:Influenza in Birds / Q000821:virology; D007251:Influenza, Human / Q000821:virology; D019158:N-Acetylneuraminic Acid / Q000737:chemistry / Q000378:metabolism; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D005697:Galactosides; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid