期刊
GLYCOCONJUGATE JOURNAL
卷 26, 期 1, 页码 99-109出版社
SPRINGER
DOI: 10.1007/s10719-008-9169-x
关键词
Sialoglycoconjugates; Influenza virus; Hemagglutinin; Neuraminidase; Oligosaccharide specificity
资金
- Russian Foundation for Basic Research [07-04-00663, 06-04-48085]
- Russian Academy of Sciences Presidium Program Molecular and Cell Biology
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 alpha 2-3-sialylated carbohydrate chains, while human virus HA interacts with alpha 2-6 chains and low-active NA cleaves both alpha 2-3- and alpha 2-6-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, SiaLe(c), SiaLe(a), SiaLe(x), 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 alpha 2-3-sialosides and the appearance of affinity for alpha 2-6-sialosides (H3N2 reassortant), or to decreasing the HA affinity for SiaLe(c) and SiaLe(a) (H3N1 reassortant), or to enhancing the ability of NA to discriminate between alpha 2-3/2-6 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.
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