Glycoconjugate Journal

, Volume 26, Issue 1, pp 99–109 | Cite as

Adjustment of receptor-binding and neuraminidase substrate specificties in avian–human reassortant influenza viruses

  • Yulia Shtyrya
  • Larisa Mochalova
  • Galina Voznova
  • Irina Rudneva
  • Aleksandr Shilov
  • Nikolai Kaverin
  • Nicolai Bovin


Balanced action of hemagglutinin (HA) and neuraminidase (NA) is an important condition of influenza virus efficient replication, but a role of HA and NA specificities at oligosaccharide level in maintaining such a balance remains poorly studied. Avian virus HA binds exclusively and NA digests efficiently α2–3-sialylated carbohydrate chains, while human virus HA interacts with α2–6 chains and low-active NA cleaves both α2–3- and α2–6-sialosides. Reassortment between viruses leading to appearance of avian virus HA and human virus NA on the virion surface often resulted in decreasing the replicative potential of the formed variants because of disturbance of a functional balance between “alien” HA and NA. A restoration of the reassortant productivity happened due to the appearance of amino acid substitutions in HA and, sometimes, NA. Here, a role of NA and HA oligosaccharide specificities in a restoration of HA–NA functional balance in high-yield passage variants was studied. Postreassortment changes in HA receptor-binding and NA substrate specificities for three reassortant/passage variant virus pairs towards 3′SiaLac, 3′SiaLacNAc, SiaLec, SiaLea, SiaLex, 6′SiaLac, and 6′SiaLacNAc were determined. Selection of the high-yield variants of the human-avian reassortants led either to twofold decrease in the affinity of HA for most α2–3-sialosides and the appearance of affinity for α2–6-sialosides (H3N2 reassortant), or to decreasing the HA affinity for SiaLec and SiaLea (H3N1 reassortant), or to enhancing the ability of NA to discriminate between α2–3/2–6 substrates (H4N1 reassortant). Thus, all postreassortment changes in oligosaccharide specificities of “alien” HA and NA were directed towards their adjustment to each other, but by different manner.


Sialoglycoconjugates Influenza virus Hemagglutinin Neuraminidase Oligosaccharide specificity 





4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionic acid


bovine serum albumin




hemagglutinating unit


dissociation constant


affinity constant




N-acetylneuraminic acid






initial substrate concentration


initial rate of enzymatic hydrolysis



















TN buffer

0.02 M tris-HCl, pH 7.2, with 0.1 M NaCl



The work was supported by grants of Russian Foundation for Basic Research 07-04-00663 and 06-04-48085, and the Russian Academy of Sciences Presidium Program “Molecular and Cell Biology”.


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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Yulia Shtyrya
    • 1
  • Larisa Mochalova
    • 1
    • 2
  • Galina Voznova
    • 1
  • Irina Rudneva
    • 3
  • Aleksandr Shilov
    • 3
  • Nikolai Kaverin
    • 3
  • Nicolai Bovin
    • 1
  1. 1.Russian Academy of SciencesShemyakin and Ovchinnikov Institute of Bioorganic ChemistryMoscowRussia
  2. 2.Russian Academy of SciencesEngelhardt Institute of Molecular BiologyMoscowRussia
  3. 3.Russian Academy of Medical SciencesD. I. Ivanovsky Institute of VirologyMoscowRussia

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