1887

Abstract

The virulent influenza virus clone 7a produced a greater level of apoptosis in MDCK cells compared with the attenuated strain A/Fiji. In both cases, apoptosis could be partially blocked by treatment with three anti-neuraminidase compounds [4-amino-(GR121158A) and 4-guanidino-(GG167; Zanamivir) 2,3-dehydro-N-acetylneuraminic acid and 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA)] when they were given to cells during the virus attachment/entry phase, but not subsequent to this phase. In contrast, GG167, which does not enter cells, did not affect the numbers of infected cells and, in addition, acted late in the infection cycle to inhibit virus yields. Clone 7a neuraminidase was more active than A/Fiji neuraminidase when fetuin was used as the substrate. Similar differences in activity between the two viruses were seen when alpha-2,6 sialyl lactose was used as a substrate, but not with alpha-2,3 sialyl lactose. No sequence differences in the enzyme active site of the two neuraminidases were observed, indicating that differences in neuraminidase specificity and activity may be dictated by other residues. These results suggest that neuraminidase plays some role in the induction of apoptosis and that it acts prior to or during virus entry. However, apoptosis was considerably reduced when UV-irradiated virus, which retains >75% of its neuraminidase activity, was used. In addition, ammonium chloride, used to prevent virus entry, reduced virus-induced apoptosis. Amantadine, which inhibits virus uncoating, also inhibited apoptosis induced by the amantadine-sensitive strain A/Udorn/307/72 (H3N2), but not the amantadine-resistant clone 7a. Hence, one or more intracellular processes are also involved in influenza virus-induced apoptosis.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-80-1-137
1999-01-01
2022-05-25
Loading full text...

Full text loading...

/deliver/fulltext/jgv/80/1/0800137a.html?itemId=/content/journal/jgv/10.1099/0022-1317-80-1-137&mimeType=html&fmt=ahah

References

  1. Adeyfa C. A. O., Quayle K., McCauley J. W. 1994; A rapid method for the analysis of influenza virus genes: application to the reassortment of equine influenza virus genes. Virus Research 32:391–399
    [Google Scholar]
  2. Aminoff D. 1961; Methods for the quantitative estimation of N-acetylneuraminic acid and their application to hydrolysates of sialmucoids. Biochemistry Journal 81:384–392
    [Google Scholar]
  3. Aymard-Henry M., Coleman M. T., Dowdle W. R., Laver W. G., Schild G. C., Webster R. G. 1973; Influenza virus neuraminidase and neuraminidase-inhibition test procedures. Bulletin of the World Health Organization 48:199–202
    [Google Scholar]
  4. Baldwin A. S. J. 1996; The NF-kB and Ik B proteins: new discoveries and insights. Annual Review of Immunology 14:649–681
    [Google Scholar]
  5. Bentley D. R., Brownlee G. G. 1982; Sequence of the N2 neuraminidase from influenza virus A/NT/60/68. Nucleic Acid Research 10:5033–5042
    [Google Scholar]
  6. Blanchetta F., Day R., Dong W., Laprise M.-H., Dubois C. M. 1997; TGFβ1 regulates gene expression of its own converting enzyme furin. Journal of Clinical Investigation 99:1974–1983
    [Google Scholar]
  7. Brunner A. M., Gentry L. M., Cooper J. A., Purchio A. F. 1988; Recombinant type 1 transforming growth factor p precursor produced in Chinese hamster ovary cells is glycosylated and phosphorylated. Molecular and Cellular Biology 8:2229–2232
    [Google Scholar]
  8. Colman P. M., Varghese J. N., Laver W. G. 1983; Structure of the catalytic and antigenic sites in influenza virus neuraminidase. Nature 303:41–44
    [Google Scholar]
  9. Compans R. W., Dimmock N. J., Meier-Ewert H. 1969; Effect of antibody to neuraminidase on the maturation and hemagglutinating activity of an influenza A2 virus. Journal of Virology 4:528–534
    [Google Scholar]
  10. Devereux J., Haeberli P., Smithies O. 1984; A comprehensive set of sequence-analysis programs for the vax. Nucleic Acids Research 12:387–395
    [Google Scholar]
  11. Els M. C., Air G. M., Murti K. G., Webster R. G., Laver W. G. 1985; An 18-amino acid deletion in an influenza neuraminidase. Virology 142:241–247
    [Google Scholar]
  12. Fesq H., Bacher M., Nain M., Gemsa D. 1994; Programmed cell-death (apoptosis) in human monocytes infected by influenza A virus. Immunobiology 190:175–182
    [Google Scholar]
  13. Gitelman S. E., Dernyck R. 1994; Transforming growth factor-P (TGF-p). In Guidebook to Cytokines and their Receptors pp 223–226 Edited by Nicola N. A. Oxford: Sambrook & Tooze;
    [Google Scholar]
  14. Govorkova E. A., Murti G., Meignier B., Detaisne C., Webster R.G. 1996; African green monkey kidney (Vero) cells provide an alternative host cell system for influenza A and influenza B viruses. Journal of Virology 70:5519–5524
    [Google Scholar]
  15. Gubareva L. V., Bethell R. C., Penn C. R., Webster R. G. 1996; In vitro characterization of 4-guanidino-Neu5Ac2en-resistant mutants of influenza A virus. In Proceedings of the Third International Conference on Options for the Control ofInfluenza pp 753–760 Edited by Brown E. L. Hampson A. W., Webster R. G. Amsterdam: Elsevier;
    [Google Scholar]
  16. Hinshaw V. S., Olsen C. W., Dybdahl-Sissoko N., Evans D. 1994; Apoptosis: a mechanism of cell-killing by influenza A and influenza B viruses. Journal of Virology 68:3667–3673
    [Google Scholar]
  17. Jacobs B. L., Langland J. O. 1996; When two strands are better than one: the mediators and modulators of the cellular responses to double-stranded RNA. Virology 219:339–349
    [Google Scholar]
  18. Jakeman K. J., Smith H., Sweet C. 1991; Influenza virus enhancement of membrane leakiness induced by staphylococcal a toxin, diphtheria toxin and streptolysin S. Journal of General Virology 72:111–115
    [Google Scholar]
  19. Jamaluddin M., Garolfalo R., Ogra P. L., Brasier A. R. 1996; Inducible translational regulation of the NF-IL6 transcription factor by respiratory syncytial virus infection in pulmonary epithelial cells. Journal of Virology 70:1554–1563
    [Google Scholar]
  20. Kawaoka Y. 1991; Structural features influencing hemagglutinin cleavability in a human influenza A virus. Journal of Virology 65:1195–1201
    [Google Scholar]
  21. Knaus P. I., Lodish H. F. 1994; Receptors for transforming growth factor-P (TGF-β). In Guidebook to Cytokines and their Receptors pp 227–231 Edited by Nicola N. A. Oxford: Sambrook & Tooze;
    [Google Scholar]
  22. Kumar S. 1995; ICE-like proteases in apoptosis. Trends in Biochemical Sciences 20:198–202
    [Google Scholar]
  23. Lenardo M. J., Baltimore D. 1989; NF-kB: a pleiotropic mediator of inducible and tissue-specific gene control. Cell 58:227–229
    [Google Scholar]
  24. Liu C., Eichelberger M. C., Compans R. W., Air G. M. 1995; Influenza type A virus neuraminidase does not play a role in viral entry, replication, assembly, or budding. Journal of Virology 69:1099–1106
    [Google Scholar]
  25. Lowy R. J., Dimitrov D. S. 1997; Characterization of influenza virus-induced death in J774.1 macrophages. Experimental Cell Research 234:249–258
    [Google Scholar]
  26. Lu Y., Wambach M., Katze M. G., Krug R. M. 1995; Binding of influenza virus NS1 protein to double-stranded RNA inhibits the activation of the protein kinase that phosphorylates the eIF-2 translation initiation factor. Virology 214:222–228
    [Google Scholar]
  27. McDonald P. P., Bald A., Cassatella M. A. 1997; Activation of the nf-kb pathway by inflammatory stimuli in human neutrophils. Blood 89:3421–3433
    [Google Scholar]
  28. Matsuyama T., Sweet C., Collie M. H., Smith H. 1980; Aspects of virulence in ferrets exhibited by influenza virus recombinants of known genetic constitution. Journal of Infectious Diseases 141:351–361
    [Google Scholar]
  29. Palese P., Compans R. W. 1976; Inhibition of influenza virus replication in tissue culture by 2-deoxy-2, 3-dehydro-N-trifluoroacetyl-neuraminic acid (FANA): mechanism of action. Journal of General Virology 33:159–163
    [Google Scholar]
  30. Palese P., Tobita K., Ueda M., Compans R. W. 1974; Characterization of temperature-sensitive influenza virus mutants defective in neuraminidase. Virology 61:397–410
    [Google Scholar]
  31. Pickering J. M., Smith H., Sweet C. 1992; Influenza virus pyrogenicity: central role of structural orientation of virion components and involvement of viral lipid and glycoproteins. Journal of General Virology 73:1345–1354
    [Google Scholar]
  32. Price G. E., Fenton R. J., Smith H., Sweet C. 1997a; Are known pyrogenic cytokines responsible for fever in influenza?. Journal of Medical Virology 52:336–340
    [Google Scholar]
  33. Price G. E., Smith H., Sweet C. 1997b; Differential induction of cytotoxicity and apoptosis by influenza virus strains of differing virulence. Journal of General Virology 78:2821–2829
    [Google Scholar]
  34. Ryan D. M., Ticehurst J., Dempsey M. H. 1995; GG167 (4-guanidino-2, 4-dideoxy-2, 3-dehydro-N-acetylneuraminic acid) is a potent inhibitor of influenza virus in ferrets. Antimicrobial Agents and Chemotherapy 39:2583–2584
    [Google Scholar]
  35. Schreier E., Roeske H., Driesel G., Kunkel U., Petzfold D. R., Berlinghoff R., Michel S. 1988; Complete nucleotide sequence of the neuraminidase gene of the human influenza virus A/Chile/1/83. Archives of Virology 99:271–276
    [Google Scholar]
  36. Schultz-Cherry S., Hinshaw V. S. 1996; Influenza virus neuraminidase activates latent transforming growth-factor β. Journal of Virology 70:8624–8629
    [Google Scholar]
  37. Schultz-Cherry S., Krug R. M., Hinshaw V. S. 1998; Induction of apoptosis by influenza virus. Seminars in Virology 8:491–495
    [Google Scholar]
  38. Sweet C., Stephen J., Smith H. 1974; Purification of influenza viruses using disulphide-linked immunosorbents derived from rabbit antibody. Immunochemistry 11:295–304
    [Google Scholar]
  39. Takizawa T., Matsukawa S., Higuchi Y., Nakamura S., Nakanishi Y., Fukuda R. 1993; Induction of programmed cell death (apoptosis) by influenza virus infection in tissue culture cells. Journal of General Virology 74:2347–2355
    [Google Scholar]
  40. Takizawa T., Fukuda R., Miyawaki T., Ohashi K., Nakanishi Y. 1995; Activation of the apoptotic fas antigen-encoding gene upon influenza virus infection involving spontaneously produced beta-interferon. Virology 209:288–296
    [Google Scholar]
  41. Takizawa T., Ohashi K., Nakanishi Y. 1996; Possible involvement of double stranded RNA-activated protein kinase in cell death by influenza virus infection. Journal of Virology 70:8128–8132
    [Google Scholar]
  42. Varghese J. N., Laver W. G., Colman P. M. 1983; Structure of the influenza virus glycoprotein antigen neuraminidase at 2.9 Å resolution. Nature 303:35–40
    [Google Scholar]
  43. von Itzstein M., Wu W.-Y., Kok G. B., Pegg M. S., Dyason J. C., Jin B., Phan T. V., Smythe M. L., White H. F., Oliver S. W., Colman P. M., Varghese J. N., Ryan D. M., Woods J. M., Bethell R. C., Hotham V. J., Cameron J. M., Penn C. R. 1993; Rational design of potent sialidase-based inhibitors of influenza virus replication. Nature 363:418–423
    [Google Scholar]
  44. Wada N., Matsumura M., Oba Y., Kobayashi N., Takizawa T., Nakanishi Y. 1995; Transcription stimulation of the Fas-encoding gene by nuclear factor for interleukin-6 expression upon influenza virus infection. Journal of Biological Chemistry 270:18007–18012
    [Google Scholar]
  45. Wharton S. A., Belshe R. B., Skehel J. J., Hay A. J. 1994; Role of virion M2 protein in influenza virus uncoating: specific reduction in the rate of membrane fusion between virus and liposomes by amantadine. Journal of General Virology 75:945–948
    [Google Scholar]
  46. Woods J. M., Bethell R. C., Coates J. A. V., Healy N., Hiscox S. A., Pearson B. A., Ryan D. M., Ticehurst J., Tilling J., Walcott S. M., Penn C. R. 1993; 4-guanidino-2, 4-dideoxy-2, 3-dehydro-N-acetyl-neuraminic acid is a highly effective inhibitor both of the sialidase (neuraminidase) and of growth of a wide range of influenza A and influenza B viruses in vitro. Antimicrobial Agents and Chemotherapy 37:1473–1479
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-80-1-137
Loading
/content/journal/jgv/10.1099/0022-1317-80-1-137
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