1887

Abstract

The locations of amino acid positions relevant to antigenic variation in the nucleoprotein (NP) of influenza virus are not conclusively known. We analysed the antigenic structure of influenza A virus NP by introducing site-specific mutations at amino acid positions presumed to be relevant for the differentiation of strain differences by anti-NP monoclonal antibodies. Mutant proteins were expressed in a prokaryotic system and analysed by performing ELISA with monoclonal antibodies. Four amino acid residues were found to determine four different antibody-binding sites. When mapped in a 3D X-ray model of NP, the four antigenically relevant amino acid positions were found to be located in separate physical sites of the NP molecule.

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2009-07-01
2019-10-13
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References

  1. Carragher, D. M., Kaminski, D. A., Moquin, A., Hartson, L. & Randall, T. D. ( 2008; ). A novel role for non-neutralizing antibodies against nucleoprotein in facilitating resistance to influenza virus. J Immunol 181, 4168–4176.[CrossRef]
    [Google Scholar]
  2. Fu, T.-M., Friedman, A., Ulmer, J. B., Liu, M. A. & Donnelly, J. J. ( 1997; ). Protective cellular immunity: cytotoxic T-lymphocyte responses against dominant and recessive epitopes of influenza virus nucleoprotein induced by DNA immunization. J Virol 71, 2715–2721.
    [Google Scholar]
  3. Herlocher, M. L., Bucher, D. & Webster, R. G. ( 1992; ). Host range determination and functional mapping of the nucleoprotein and matrix genes of influenza viruses using monoclonal antibodies. Virus Res 22, 281–293.[CrossRef]
    [Google Scholar]
  4. Kreijtz, J. H., de Mutsert, G., van Baalen, C. A., Fouchier, R. A. M., Osterhaus, A. D. M. E. & Rimmelzwaan, G. F. ( 2008; ). Cross-recognition of avian H5N1 influenza virus by human cytotoxic T-lymphocyte populations directed to human influenza A virus. J Virol 82, 5161–5166.[CrossRef]
    [Google Scholar]
  5. Ng, A. K.-L., Zhang, H., Tan, K., Li, Z., Liu, J. H., Chan, P. K., Li, S. M., Chan, W. Y., Au, S. W. & other authors ( 2008; ). Structure of the influenza virus A H5N1 nucleoprotein: implications for RNA binding, oligomerization and vaccine design. FASEB J 22, 3638–3647.[CrossRef]
    [Google Scholar]
  6. Philpott, M., Easterday, B. C. & Hinshaw, V. ( 1989; ). Neutralizing epitopes of the H5 hemagglutinin from a virulent avian influenza virus and their relationships to pathogenicity. J Virol 63, 3453–3458.
    [Google Scholar]
  7. Portela, A. & Digard, P. ( 2002; ). The influenza virus nucleoprotein: a multifunctional RNA-binding protein pivotal to virus replication. J Gen Virol 83, 723–734.
    [Google Scholar]
  8. Prokudina, E. N., Semenova, N., Chumakov, V. & Stitz, L. ( 2008; ). An antigenic epitope of influenza virus nucleoprotein (NP) associated with polymeric forms of NP. Virol J 5, 37 [CrossRef]
    [Google Scholar]
  9. van Wyke, K. L., Hinshaw, V. S., Bean, W. J. & Webster, R. G. ( 1980; ). Antigenic variation of influenza A virus nucleoprotein detected with monoclonal antibodies. J Virol 35, 24–30.
    [Google Scholar]
  10. van Wyke, K. L., Bean, W. J. & Webster, R. G. ( 1981; ). Monoclonal antibodies to the influenza A virus nucleoprotein affecting RNA transcription. J Virol 39, 313–317.
    [Google Scholar]
  11. Varich, N. L. & Kaverin, N. V. ( 2004; ). Antigenically relevant amino acid positions as revealed in reactions of monoclonal antibodies with the nucleoproteins of closely related influenza A virus strains. Arch Virol 149, 2271–2276.[CrossRef]
    [Google Scholar]
  12. Voeten, J. T. M., Bestebroer, T. M., Nieuwkoop, N. J., Fouchier, R. A. M., Osterhaus, A. D. M. E. & Rimmelzwaan, G. F. ( 2000; ). Antigenic drift in the influenza A virus (H3N2) nucleoprotein and escape from recognition by cytotoxic T lymphocytes. J Virol 74, 6800–6807.[CrossRef]
    [Google Scholar]
  13. Yang, M., Berhane, Y., Salo, T., Li, M., Hole, K. & Clavijo, A. ( 2008; ). Development and application of monoclonal antibodies against avian influenza virus nucleoprotein. J Virol Methods 147, 265–274.[CrossRef]
    [Google Scholar]
  14. Ye, Q., Krug, R. M. & Tao, Y. J. ( 2006; ). The mechanism by which influenza A virus nucleoprotein forms oligomers and binds RNA. Nature 444, 1078–1082.[CrossRef]
    [Google Scholar]
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vol. , part 7, pp. 1730–1733

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