Advertisement

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
Article

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 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.

Keywords

Sialoglycoconjugates Influenza virus Hemagglutinin Neuraminidase Oligosaccharide specificity 

Abbreviations

biot

biotin

BODIPY

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

BSA

bovine serum albumin

HA

hemagglutinin

HAU

hemagglutinating unit

Kd

dissociation constant

Kaff

affinity constant

NA

neuraminidase

Neu5Ac

N-acetylneuraminic acid

OS

oligosaccharide

PAA

polyacrylamide

S0

initial substrate concentration

V0

initial rate of enzymatic hydrolysis

3′SiaLac

Neu5Acα2–3Galβ1–4Glc

3′SiaLacNAc

Neu5Acα2–3Galβ1–4GlcNAc

6′SiaLac

Neu5Acα2–6Galβ1–4Glc

6′SiaLacNAc

Neu5Acα2–6Galβ1–4GlcNAc

SiaLec

Neu5Acα2–3Galβ1–3GlcNAc

SiaLea

Neu5Acα2–3Galβ1–3(Fucα1–4)GlcNAc

SiaLex

Neu5Acα2–3Galβ1–4(Fucα1–3)GlcNAc

6Su-3′SiaLacNAc

Neu5Acα2–3Galβ1–4(6-HSO3)GlcNAc

6Su-6′SiaLacNAc

Neu5Acα2–6Galβ1–4(6-HSO3)GlcNAc

TN buffer

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

Notes

Acknowledgments

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”.

References

  1. 1.
    Barros Jr., J.F., Alviano, D.S., Silva, M.H., Wigg, M.D., Alviano, C.S., Schauer, R., et al.: Characterization of sialidase from an influenza A (H3N2) virus strain: kinetic parameters and substrate specificity. Intervirology 46, 199–206 (2003). doi: 10.1159/000072428 CrossRefGoogle Scholar
  2. 2.
    Connor, R.J., Kawaoka, Y., Webster, R.G., Paulson, J.C.: Receptor specificity in human, avian, and equine H2 and H3 influenza virus isolates. Virology 205, 17–23 (1994). doi: 10.1006/viro.1994.1615 PubMedCrossRefGoogle Scholar
  3. 3.
    Funning, T.G., Reid, A.H., Taubenberger, J.K.: Influenza A virus neuraminidase: regions of the protein potentially involved in virus-host interactions. Virology 276, 417–423 (2000). doi: 10.1006/viro.2000.0578 CrossRefGoogle Scholar
  4. 4.
    Gambaryan, A.S., Tuzikov, A.B., Piskarev, V.E., Yamnikova, S.S., Lvov, D.K., Robertson, J.S., et al.: Specification of receptor-binding phenotypes of influenza virus isolates from different hosts using synthetic sialylglycopolymers: non-egg-adapted human H1 and H3 influenza A and influenza B viruses share a common high binding affinity for 6′-sialyl(N-acetyllactosamine). Virology 232, 345–350 (1997). doi: 10.1006/viro.1997.8572 PubMedCrossRefGoogle Scholar
  5. 5.
    Ilyushina, N.A., Rudneva, I.A., Shilov, A.A., Klenk, H.-D., Kaverin, N.V.: Postreassortment changes in a model system: HA-NA adjustment in an H3N2 avian–human reassortant influenza virus. Arch. Virol. 150, 1327–1338 (2005). doi: 10.1007/s00705-005-0490-4 PubMedCrossRefGoogle Scholar
  6. 6.
    Kaverin, N.V., Gambaryan, A.S., Bovin, N.V., Rudneva, I.A., Shilov, A.A., Khodova, O.M., et al.: Postreassortment changes in influenza A virus hemagglutinin restoring HA-NA functional match. Virology 244, 315–321 (1998). doi: 10.1006/viro.1998.9119 PubMedCrossRefGoogle Scholar
  7. 7.
    Kaverin, N.V., Matrosovich, M.N., Gambaryan, A.S., Rudneva, I.A., Shilov, A.A., Varich, N.L., et al.: Intergenic HA-NA interactions in influenza A virus: postreassortment substitutions of charged amino acid in the hemagglutinin of different subtypes. Virus Res. 66, 123–129 (2000). doi: 10.1016/S0168-1702(99)00131-8 PubMedCrossRefGoogle Scholar
  8. 8.
    Kilbourne, E.D.: Influenza. Plenum, New York (1987)Google Scholar
  9. 9.
    Kobasa, D., Kodihalli, S., Luo, M., Castrucci, M.R., Donatelli, I., Suzuki, Y., et al.: Amino acid resides contributing to the substrate specificity of the influenza A virus neuraminidase. J. Virol. 73, 6743–6751 (1999)PubMedGoogle Scholar
  10. 10.
    Kobasa, D., Wells, K., Kawaoka, Y.: Amino acids responsible for the absolute sialidase activity of the influenza virus neuraminidase: relationship to growth in the duck intestine. J. Virol. 75, 11773–11778 (2001). doi: 10.1128/JVI.75.23.11773-11780.2001 PubMedCrossRefGoogle Scholar
  11. 11.
    Kumari, K., Gulati, S., Smith, D.F., Gulati, U., Cumming, R.D., Air, G.M.: Receptor binding specificity of recent human H3N2 influenza viruses. Virol. J. 4, 42 (2007). doi: 10.1186/1743-422X-4-42 PubMedCrossRefGoogle Scholar
  12. 12.
    Liu, C., Eichelberger, M.C., Compans, R.W., Air, G.M.: Influenza type A virus neuraminidase does not play a role in virus entry, replication, assembly, or budding. J. Virol. 69, 1099–1106 (1995)PubMedGoogle Scholar
  13. 13.
    Matrosovich, M., Matrosovich, T., Gray, T., Roberts, N.A., Klenk, H.-D.: Neuraminidase is important for the initiation of influenza virus infection in human airway epithelium. J. Virol. 78, 12665–12667 (2004). doi: 10.1128/JVI.78.22.12665-12667.2004 PubMedCrossRefGoogle Scholar
  14. 14.
    Matrosovich, M.N., Klenk, H.-D., Kawaoka, Y.: Receptor specificity, host-range, and pathogenicity of influenza viruses. In: Kawaoka, Y. (ed.) Influenza Virology: Current Topics, pp. 95–137. Caister, Norfolk (2006)Google Scholar
  15. 15.
    Mitnaul, L.J., Matrosovich, M.N., Castrucci, M.R., Tuzikov, A.B., Bovin, N.V., Kobasa, D., et al.: Balanced hemagglutinin and neuraminidase activities are critical for replication of influenza A virus. J. Virol. 74, 6015–6020 (2000). doi: 10.1128/JVI.74.13.6015-6020.2000 PubMedCrossRefGoogle Scholar
  16. 16.
    Mochalova, L., Gambaryan, A., Romanova, J., Tuzikov, A., Chinarev, A., Katinger, D., et al.: Receptor-binding properties of modern human influenza viruses primarily isolated in Vero and MDCK cells and chicken embryonated eggs. Virology 313, 437–480 (2003). doi: 10.1016/S0042-6822(03)00377-5 CrossRefGoogle Scholar
  17. 17.
    Mochalova, L.V., Korchagina, E.Y., Kurova, V.S., Shtyrya, J.A., Gambaryan, A.S., Bovin, N.V.: Fluorescent assay for studying the substrate specificity of neuraminidase. Anal. Biochem. 34, 190–193 (2005). doi: 10.1016/j.ab.2005.02.019 CrossRefGoogle Scholar
  18. 18.
    Mochalova, L., Kurova, V., Shtyrya, J., Korchagina, E., Gambaryan, A., Belyanchikov, I., et al.: Oligosaccharide specificity of influenza H1N1 virus neuraminidases. Arch. Virol. 152, 2047–2057 (2007). doi: 10.1007/s00705-007-1024-z PubMedCrossRefGoogle Scholar
  19. 19.
    Palese, P., Tobita, K., Ueda, M., Compans, R.W.: Characterization of temperature-sensitive influenza virus mutants defective in neuraminidase. Virology 61, 397–410 (1974). doi: 10.1016/0042-6822(74)90276-1 PubMedCrossRefGoogle Scholar
  20. 20.
    Pazynina, G., Tuzikov, A., Chinarev, A., Obukhova, P., Bovin, N.: Simple stereoselective synthesis of alfa2–6 sialo-oligosaccharides. Tetrahedron Lett. 43, 8011–8013 (2002). doi: 10.1016/S0040-4039(02)01983-4 CrossRefGoogle Scholar
  21. 21.
    Pazynina, G.V., Sablina, M.A., Tuzikov, A.B., Chinarev, A.A., Bovin, N.V.: Synthesis of complex 2–3 sialo-oligosaccharides, including sulfated and fucosylated ones, using Neu5Ac alfa2–3Gal as a building block. Mendeleev Commun. 13, 245–248 (2003). doi: 10.1070/MC2003v013n06ABEH001845 CrossRefGoogle Scholar
  22. 22.
    Rudneva, I.A., Kovaleva, V.P., Varich, N.L., Farashyan, V.R., Gubareva, L.V., Yamnikova, S.S., et al.: Influenza A virus reassortants with surface glycoprotein genes of the avian parent viruses: effects of HA and NA gene combinations on virus aggregation. Arch. Virol. 133, 437–450 (1993). doi: 10.1007/BF01313781 PubMedCrossRefGoogle Scholar
  23. 23.
    Rudneva, I.A., Sklyanskaya, E.I., Barulina, O.S., Yamnikova, S.S., Kovaleva, V.P., Tsvetkova, I.V., et al.: Phenotypic expression of HA-NA combinations in human-avian influenza A virus reassortants. Arch. Virol. 141, 1091–1099 (1996). doi: 10.1007/BF01718612 PubMedCrossRefGoogle Scholar
  24. 24.
    Shtyrya, Y., Mochalova, L., Gambarayn, A., Korchagina, E., Xu, X., Klimov, A., et al: Neuraminidases of H9N2 influenza viruses isolated from different hosts display various substrate specificity. In Options for the control of influenza VI Conference, p.14. Toronto (2007)Google Scholar
  25. 25.
    Suzuki, Y., Kato, H., Naeve, W., Webster, R.: Single-amino-acid Substitution in an antigenic site of influenza virus hemagglutinin can alter the specificity of binding to cell membrane-associated gangliosides. J. Virol. 63, 4298–4302 (1989)PubMedGoogle Scholar
  26. 26.
    Tumpey, T.M., Maines, T.R., Hoeven, N.V., Glaser, L., Solorzano, A., Pappas, C., et al.: A two-amino acid change in the hemagglutinin of the 1918 influenza virus abolishes transmission. Science 315, 655–659 (2007). doi: 10.1126/science.1136212 PubMedCrossRefGoogle Scholar
  27. 27.
    Tuzikov, A.B., Gambaryan, A.S., Juneja, L.R., Bovin, N.V.: Conversion of complex sialo-oligosaccharides into polymeric conjugates and their anti-influenza virus inhibitory potency. J. Carbohydr. Chem. 19, 1191–1200 (2000). doi: 10.1080/07328300008544143 CrossRefGoogle Scholar
  28. 28.
    Varghese, J.N., Colman, P.M., van Donkelaar, A., Blick, T.J., Sharasrabudhi, A.: McKimm –Breshkin JL, Structural evidence for a second sialic acid binding site in avian influenza virus neuraminidases. Biochemistry 94, 11808–11812 (1997)Google Scholar
  29. 29.
    Wagner, R., Wolff, T., Herwig, A., Pleschka, S., Klenk, H.-D.: Interdependence of hemagglutinin glycosylation and neuraminidase as regulators of influenza virus growth: a study by reverse genetics. J. Virol. 74, 6316–6323 (2000). doi: 10.1128/JVI.74.14.6316-6323.2000 PubMedCrossRefGoogle Scholar
  30. 30.
    Wagner, R., Matrosovich, M., Klenk, H.-D.: Functional balance between hemagglutinin and neuraminidase in influenza virus infections. Rev. Med. Virol. 12, 159–166 (2002). doi: 10.1002/rmv.352 PubMedCrossRefGoogle Scholar

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

Personalised recommendations