9tq8 | pdb_00009tq8
Neuraminidase NA isolated from the H1N1 strain A/Victoria/2570/2019 propagated in eggs in complex with zanamivir
Structural highlights
FunctionA0A6C0SG80_9INFA Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus release. Additionally helps virus spread through the circulation by further removing sialic acids from the cell surface. These cleavages prevent self-aggregation and ensure the efficient spread of the progeny virus from cell to cell. Otherwise, infection would be limited to one round of replication. Described as a receptor-destroying enzyme because it cleaves a terminal sialic acid from the cellular receptors. May facilitate viral invasion of the upper airways by cleaving the sialic acid moities on the mucin of the airway epithelial cells. Likely to plays a role in the budding process through its association with lipid rafts during intracellular transport. May additionally display a raft-association independent effect on budding. Plays a role in the determination of host range restriction on replication and virulence. Sialidase activity in late endosome/lysosome traffic seems to enhance virus replication.[HAMAP-Rule:MF_04071] Publication Abstract from PubMedSeasonal influenza vaccines are produced using viruses containing the hemagglutinin (HA) and neuraminidase (NA) antigens. However, NA amounts have not been monitored for more than 50 years due to lack of strategies for isolating NA reference antigens from viruses, limiting the ability to evaluate any contributions from NA. Here, we developed an influenza neuraminidase active-site affinity chromatography (INAAC) strategy that uses an active-site binding antibody to isolate functional NAs from influenza A and B vaccine strains. INAAC recovered 20-60% of detergent-solubilized NA activity from vaccine viruses and recombinant sources, with CaCl(2) elution proving most effective. ELISA results with the isolated NA from the H1N1 strain and recombinant full-length N1 showed that a commercial vaccine contains functional N1 and H1 at a ratio of approximately 1:10. Structure determination by cryo-electron microscopy confirmed the native tetrameric conformation of the isolated N1 and provided insight into the stalk conformation of a virus-derived NA. Finally, comparative analyses of NAs isolated from recent egg-propagated vaccine strains (H1N1, H3N2 and type B) revealed a unique proteolytic susceptibility of type B NA and strain-specific differences in sialic acid affinities and catalytic rates. These results demonstrate that INAAC supports multiple applications from NA structural analysis to producing NA vaccine antigens and reference standards, addressing longstanding challenges for incorporating NA into influenza vaccine development and quality control. INAAC: An affinity chromatography strategy enabling characterization and quantification of influenza neuraminidase antigens in vaccines.,Kang H, Borowska A, Kanai T, Gao J, Yu H, Chen X, Gorman J, Slotboom DJ, Daniels R J Biol Chem. 2026 May 11:113138. doi: 10.1016/j.jbc.2026.113138. PMID:42119981[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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