title: Adjustment of receptor-binding and neuraminidase substrate specificities in avian-human reassortant influenza viruses.
abstract: 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 alpha2-3-sialylated carbohydrate chains, while human virus HA interacts with alpha2-6 chains and low-active NA cleaves both alpha2-3- and alpha2-6-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 alpha2-3-sialosides and the appearance of affinity for alpha2-6-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 alpha2-3/2-6 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.
authors.affiliation: Russian Academy of Sciences, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997 Moscow, Russia. saj1@yandex.ru
authors.forename: Yulia
authors.initials: Y
authors.lastname: Shtyrya
authors.forename: Larisa
authors.initials: L
authors.lastname: Mochalova
authors.forename: Galina
authors.initials: G
authors.lastname: Voznova
authors.forename: Irina
authors.initials: I
authors.lastname: Rudneva
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Shilov
authors.forename: Nikolai
authors.initials: N
authors.lastname: Kaverin
authors.forename: Nicolai
authors.initials: N
authors.lastname: Bovin
mesh_terms: D000818:Animals; D001717:Birds; D006388:Hemagglutinins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D009980:Influenza A virus / Q000201:enzymology*; D009439:Neuraminidase / Q000737:chemistry* / Q000378:metabolism; D009844:Oligosaccharides / Q000737:chemistry* / Q000378:metabolism; D011991:Receptors, Virus / Q000737:chemistry* / Q000378:metabolism; D013045:Species Specificity; D013379:Substrate Specificity; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D006388:Hemagglutinins; D009844:Oligosaccharides; D011991:Receptors, Virus; D014764:Viral Proteins; D009439:Neuraminidase