1887

Abstract

Summary

An analysis of the nucleoprotein (NP) of 29 different influenza A viruses by phosphopeptide fingerprinting revealed three prototype patterns. The first, which was a complex pattern consisting of six to seven phosphopeptides, another which was relatively simple consisted of two or three phosphopeptides, and a third one which was complex but was missing the main phosphopeptide shared by the two other patterns. Phosphoserine was the only labelled phosphamino acid detected. A tentative deduction of two of the phosphate attachment sites (serine residues at positions 3 and 473) could be made by comparison of the known amino acid sequences of the NPs of 25 strains. No correlation was found between species specificity or subtype or year of isolation of the strains. During the infectious cycle the fingerprint underwent significant changes, indicating subtle phosphorylation and dephosphorylation of the NP at various stages during viral multiplication. Most of the phosphopeptides were metabolically stable; however one major phosphopeptide, which was not found in the NP of mature virions, exhibited a high turnover (presumably serine at position 3). The phosphopeptide fingerprint could be significantly influenced by the specific stimulation of cellular protein kinase C by the phorbol ester 12--tetradecanolyphorbol 13-acetate or by its inhibition with the isoquinoline sulphonamide H7. H7 specifically inhibited the replication of influenza A viruses by deregulation of viral protein synthesis without interfering with the multiplication of a parainfluenza virus (Newcastle disease virus), an alphavirus (Semliki Forest virus) or a flavivirus (West Nile). Therefore the correct phosphorylation of the NP of influenza viruses appears to be essential for influenza virus replication.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-70-9-2421
1989-09-01
2022-01-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/70/9/JV0700092421.html?itemId=/content/journal/jgv/10.1099/0022-1317-70-9-2421&mimeType=html&fmt=ahah

References

  1. Almond J. W., Felsenreich V. 1982; Phosphorylation of the nucleoprotein of an avian influenza virus. Journal of General Virology 60:295–305
    [Google Scholar]
  2. Breitenfeld P. M., schäfer W. 1957; The formation of fowl plague virus antigens in infected cells, as studied with fluorescent antibodies. Virology 4:328–345
    [Google Scholar]
  3. Gammelin M., Mandler J., Scholtissek C. 1989; Two subtypes of nucleoproteins (NP) of influenza A viruses. Virology 170:71–80
    [Google Scholar]
  4. Gregoriades A., Christie T., Markarian K. 1984; The membrane (M1) protein of influenza virus occurs in two forms and is a phosphoprotein. Journal cf Virology 49:225–235
    [Google Scholar]
  5. Hidaka H., Inagaki m., Kawamoto S., Sasaki Y. 1984; Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide dependent protein kinase and protein kinase C. Biochemsitry 23:5036–5041
    [Google Scholar]
  6. Hunter T. 1987; A thousand and one protein kinases. Cell 50:823–829
    [Google Scholar]
  7. Hunter T., Sefton B. M. 1980; Transforming gene product of Rous sarcoma virus phosphorylates tyrosine. Proceedings of the National Academy of SciencesU.S.A. 77:1311–1315
    [Google Scholar]
  8. Kistner O., Müller H., Becht H., Scholtissek C. 1985; Phosphopeptide fingerprints of nucleoproteins of various inflenza A virus strains grown in different host cells. Journal of General Virology 66:465–472
    [Google Scholar]
  9. LI R., Palese P., Krystal M. 1989; Complementation and analysis of an NP mutant of influenza virus. Virus Research 12:97–112
    [Google Scholar]
  10. Nishizuka Y. 1984; The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature London: 308693–698
    [Google Scholar]
  11. Petri T., Dimmock N. J. 1981; Phosphorylation of influenza virus nucleoprotein in vivo. Journal of General Virology 57:185–190
    [Google Scholar]
  12. Petri T., Patterson S., Dimmock N. J. 1982; Polymorphism of the NS1 proteins of type A influenza virus. Journal of General Virology 61:217–231
    [Google Scholar]
  13. Privalsky M. L., Penhoet E. E. 1977; Phosphorylated protein component present in influenza virions. Journal of Virology 24:401–405
    [Google Scholar]
  14. Privalsky M. L., Penhoet E. E. 1978; Influenza virus proteins: identity, synthesis, and modification analyzed by two-dimensional gel electrophoresis. Proceedings of the National Academy of SciencesU.S.A. 75:3625–3629
    [Google Scholar]
  15. Privalsky M. L., Penhoet E. E. 1981; The structure and synthesis of influenza virus phosphoproteins. Journal of Biological Chemistry 256:5368–5376
    [Google Scholar]
  16. Scholtissek C., Koennecke I., Rott R. 1978; Host range recombinants of fowl plague (influenza A) virus. Virology 91:79–85
    [Google Scholar]
  17. Scholtissek C., Müller K., Herzog S. 1986; Influence of insulin and 12-O-tetradecanoylphorbol-13-acetate (TPA) on influenza virus multiplication. Virus Research 6:287–294
    [Google Scholar]
  18. Scholtissek C., Bürger H., Kistner O., Shortridge K. F. 1987; The nucleoprotein (NP) as a possible major factor in determining host specificity of influenza H3N2 viruses of Southern China. In The Biology of Negative Strand Viruses417–423 Mahy B. W. J., Kolakofsky D. Amsterdam: Elsevier;
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-70-9-2421
Loading
/content/journal/jgv/10.1099/0022-1317-70-9-2421
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error