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

DOI: 10.1134/S0006297909120098

Cite this article as:
Gileva, I.P., Nepomnyashchikh, T.S., Ryazankin, I.A. et al. Biochemistry Moscow (2009) 74: 1356. doi:10.1134/S0006297909120098

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 factorTNF-binding proteinvariola virusviroceptorsseptic 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

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