Biochemistry (Moscow)

, Volume 74, Issue 12, pp 1356–1362

Recombinant TNF-binding protein from variola virus as a novel potential TNF antagonist

  • I. P. Gileva
  • T. S. Nepomnyashchikh
  • I. A. Ryazankin
  • S. N. Shchelkunov
Article

Abstract

Gel-filtration chromatographic separation of the lysate of Sf21 insect cells infected with recombinant baculovirus BVi67 containing the gene for TNF-binding protein (CrmB) of variola virus (VARV) revealed that hTNF-cytotoxicity neutralization activity is associated with a fraction corresponding mainly to high molecular weight proteins (above 500 kDa) and less with fractions corresponding to proteins of 270 or 90 kDa. The recombinant VARV-CrmB protein has been purified by affinity chromatography. Difference in the experimentally determined and estimated (according to amino acid composition) VARV-CrmB molecular weight is due to glycosylation of the recombinant protein expressed in the insect cells. VARV-CrmB neutralizes in vitro the cytotoxic effect of hTNF and hLTα, and its TNF-neutralizing activity is two to three orders of magnitude higher compared to the analogous effects of type I and II soluble TNF receptors, comparable with the activity of mAb MAK195, and somewhat lower than the effect of the commercial drug Remicade.

Key words

tumor necrosis factor TNF-binding protein variola virus viroceptors septic shock 

Abbreviations

aAG

α1-acid glycoprotein

CPXV

cowpox virus

Crm

cytokine response modifier

Fc

constant fragment of immunoglobulin molecule

LPS

lipopolysaccharide

LT

lymphotoxin

mAb

monoclonal antibody

MPXV

monkeypox virus

TNF

tumor necrosis factor

TNFRI(II)

tumor necrosis factor receptor type I(II)

TNFsR

soluble tumor necrosis factor receptor

VARV

variola virus

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Mc Devitt, H., Munson S., Ettingen, R., and Wu, A. (2002) Arthritis Res., 4(Suppl. 13), 141–152.CrossRefGoogle Scholar
  2. 2.
    Idriss, H. T., and Naismith, J. H. (2000) Microsc. Res. Tech., 50, 184–195.CrossRefPubMedGoogle Scholar
  3. 3.
    Bazzoni, F., and Beutler, B. (1996) N. Engl. J. Med., 334, 1717–1725.CrossRefPubMedGoogle Scholar
  4. 4.
    Nepomnyashchikh, T. S., Antonets, D. V., Gileva, I. P., and Shchelkunov, S. N. (2007) Uspekhi Sovrem. Biol., 127, 576–587.Google Scholar
  5. 5.
    Knight, D. M., Trinh, H., Le, J., Siegel, S., Shealy, D., McDonough, M., Scallon, B., Moore, M. A., Vilcek, J., Daddona, P., and Ghrayeb, J. (1993) Mol. Immunol., 30, 1443–1453.CrossRefPubMedGoogle Scholar
  6. 6.
    Siegel, S. A., Shealy, D. J., Nakada, M. T., Le, J., Woulfe, D. S., Probert, L., Kollias, G., Ghrayeb, J., Vilcek, J., and Daddona, P. E. (1995) Cytokine, 7, 15–25.CrossRefPubMedGoogle Scholar
  7. 7.
    Weinblatt, M. E., Keystone, E. C., Furst, D. E., Moreland, L. W., Weisman, M. H., Bizbara, C. A., Teoh, L. A., Fischoff, S. A., and Chartash, E. K. (2003) Arthrit. Rheumat., 48, 35–45.CrossRefGoogle Scholar
  8. 8.
    Mohler, K. M., Torrance, D. C., Smith, C. A., Goodwin, R. G., Stremler, K. E., Fung, V. P., Madani, H., and Widmer, M. B. (1993) J. Immunol., 151, 1548–1561.PubMedGoogle Scholar
  9. 9.
    Bathon, J. M., Martin, R. W., Fleischmann, R. M., Tesser, J. R., Schiff, M. H., Keystone, E. C., Genovese, M. C., Wasko, M. C., Moreland, L. W., Weaver, A. L., Harkenson, J., and Fink, B. K. (2000) N. Engl. J. Med., 343, 1586–1593.CrossRefPubMedGoogle Scholar
  10. 10.
    Lo, E., Rezaik, K., Evans, A. T., Madariaga, M. G., Phillips, M., Brobbey, W., Schwartz, D. N., Wang, Y., Weinstein, R. A., and Trenholm, G. M. (2004) Clin. Infect. Dis., 40, 636–637.Google Scholar
  11. 11.
    Arend, S. M., Breedveld, F. C., and van Dissel, J. T. (2003) Neth. J. Med., 61, 111–119.PubMedGoogle Scholar
  12. 12.
    Calabrese, L. H., Zein, N., and Vassilipoulos, D. (2004) Ann. Rheum. Dis., 63(Suppl. 2), 18–24.Google Scholar
  13. 13.
    Scallon, B. J., Trinh, T., Nedelman, M., Brennan, F. M., Feldmann, M., and Ghrayeb, J. (1995) Cytokine, 7, 759–770.CrossRefPubMedGoogle Scholar
  14. 14.
    Moreland, L. W., Baumgartner, S. W., Schiff, M. H., Tindall, E. A., Fleischmann, R. M., Weaver, A. I., Ettinger, R. E., Cohen, S., Koopman, W. J., Mohler, K., Widmer, M. B., and Blosch, C. M. (1997) N. Engl. J. Med., 337, 141–147.CrossRefPubMedGoogle Scholar
  15. 15.
    Shchelkunov, S. N. (2003) Mol. Biol. (Moscow), 37, 41–53.Google Scholar
  16. 16.
    McFadden, G., and Murphy, P. M. (2000) Curr. Opin. Microbiol., 3, 371–373.CrossRefPubMedGoogle Scholar
  17. 17.
    Gileva, I. P., Ryazankin, I. A., Maksutov, Z. A., Totmenin, A. V., Ageenko, V. A., Nesterov, A. E., and Shchelkunov, S. N. (2003) Russian Federation Patent No. 2241754. Google Scholar
  18. 18.
    Gileva, I. P., Ryazankin, I. A., Maksutov, Z. A., Totmenin, A. V., Lebedev, L. R., Nesterov, A. E., Ageenko, V. A., Shchelkunov, S. N., and Sandakhchiev, L. S. (2003) Doklady RAN, 390, 160–164.CrossRefGoogle Scholar
  19. 19.
    Lebedev, L. R., Ryazankin, I. A., Sizov, A. A., Ageenko, V. A., Odegov, V. N., Afinogenova, G. N., and Shchelkunov, S. N. (2001) Biotekhnologiya, 6, 14–18.Google Scholar
  20. 20.
    Gileva, I. P., Nepomnyashchich, T. S., Antonets, D. V., Lebedev, L. R., Kochneva, G. V., Grazhdantseva, A. A., and Shchelkunov, S. N. (2006) Biochim. Biophys. Acta, 1764, 1710–1718.PubMedGoogle Scholar
  21. 21.
    Reinhart, K., Wiegand-Lohnert, C., Grimminger, F., Kaul, M., Withington, S., Trecher, D., Eckart, J., Willatts, S., Bouza, C., Krausch, D., Stochenhuber, F., Eiselstein, J., Daum, L., and Kempeni, J. (1996) Crit. Core Med., 24, 733–742.CrossRefGoogle Scholar
  22. 22.
    Scallon, B., Cai, A., Solowski, N., Rosenberg, A., Song, X., Shealy, D., and Wagner, C. (2002) Pharmacology, 301, 418–426.Google Scholar
  23. 23.
    Bradford, M. M. (1976) Anal. Biochem., 72, 248–254.CrossRefPubMedGoogle Scholar
  24. 24.
    Laemmli, U. (1970) Nature, 227, 680–685.CrossRefPubMedGoogle Scholar
  25. 25.
    Gileva, I. P., Ryazankin, I. A., Nepomnyashchich, T. S., Totmenin, A. V., Maksyutov, Z. A., Lebedev, L. R., Afinogenova, G. N., Pustoshilova, N. M., and Shchelkunov, S. N. (2005) Mol. Biol. (Moscow), 39, 218–225.CrossRefGoogle Scholar
  26. 26.
    Aumiller, J. J., Hollister, J. R., and Jarvis, D. L. (2003) Glycobiology, 13, 497–507.CrossRefPubMedGoogle Scholar
  27. 27.
    Slade, E., Tamber, P. S., and Vincent, J.-L. (2003) Crit. Care, 7, 1–2.CrossRefPubMedGoogle Scholar
  28. 28.
    Alejo, A., Ruiz-Arguello, M. B., Ho, Y., Smith, V. P., Saraeva, M., and Alcami, A. (2006) Proc. Natl. Acad. Sci. USA, 103, 5995–6000.CrossRefPubMedGoogle Scholar
  29. 29.
    Tartaglia, A., Pennica, D., and Goeddel, D. V. (1993) J. Biol. Chem., 268, 18542–18548.PubMedGoogle Scholar
  30. 30.
    Grell, M., Douni, E., Wajant, H., Lohden, M., Clauss, M., Maxeiner, B., Georgopoulos, S., Lesslauer, W., Kollias, G., Pfizenmaier, K., and Scheurich, P. (1995) Cell, 38, 793–802.CrossRefGoogle Scholar
  31. 31.
    Hohmann, H. P., Brockhaus, M., Baeuerle, P. A., Remy, R., Kolbeck, R., and van Loon, A. P. (1990) J. Biol. Chem., 265, 22409–22417.PubMedGoogle Scholar
  32. 32.
    Medvedev, A. E., Espevik, T., Ranges, G., and Sundan, A. (1996) J. Biol. Chem., 271, 9778–9784.CrossRefPubMedGoogle Scholar
  33. 33.
    Gileva, I. P., Malkova, E. M., Nepomnyashchikh, T. S., Vinogradov, I. V., Lebedev, L. R., Kochneva, G. V., Grazhdantseva, A. A., Ryabchikova, E. I., and Shchelkunov, S. N. (2006) Cytokines Inflamm. (Russ.), 1, 44–49.Google Scholar
  34. 34.
    Sandalan, Z., Bruckheimer, E. M., Lustig, K. H., and Burstein, H. (2007) Mol. Ther., 15, 264–269.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2009

Authors and Affiliations

  • I. P. Gileva
    • 1
  • T. S. Nepomnyashchikh
    • 1
  • I. A. Ryazankin
    • 1
  • S. N. Shchelkunov
    • 1
  1. 1.FGUN State Research Center of Virology and Biotechnology VectorKoltsovo, Novosibirsk RegionRussia

Personalised recommendations