Abstract
Vaccinia virus complement control protein (VCP) was one of the first viral molecules demonstrated to have a role in blocking complement and hence in the evasion of host defense. Structurally it is very similar to the human C4b-BP and the other members of complement control protein. Functionally it is most similar to the CR1 protein. VCP blocks both major pathways of complement activation. The crystal structure of VCP was determined a little over a year ago and it is the only known structure of an intact and complete complement control protein. In addition to binding complement, VCP also binds to heparin. These two binding abilities can take place simultaneously and contribute to its many function and to its potential use in several inflammatory diseases, e.g. Alzheimer’s disease (AD), CNS injury, xenotransplantation, etc. making it a truly fascinating molecule and potential drug.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Abbreviations
- AD:
-
Alzheimer’s disease
- BP:
-
binding protein
- CP:
-
complement protein
- CR1:
-
complement receptor 1
- DAF:
-
decay accelerating factor
- FGF:
-
fibroblast growth factors
- MCP:
-
membrane cofactor protein
- SCRs:
-
short consensus repeats
- VCP:
-
vaccinia virus complement control protein
References
Alcami A, Symons J A and Smith G L 2000 The vaccinia virus soluble alpha/beta interferon (IFN) receptor binds to the cell surface and protects cells from the antiviral effects of IFN;J. Virol. 74 11230–11239
Al-Hussein K, Al-Mukhalafi Z, Pyle H R, Parhar R S, Al-Mohanna F and Lee J 2001 Detection of xenoantibodies using a simple flow cytometric assay;Xenotransplantation 8 172–175
Al-Mohanna F, Parhar R and Kotwal G J 2001 Vaccinia virus complement control protein is capable of protecting xenoen-dothelial cells from antibody binding and killing by human complement and cytotoxic cells;Transplantation 71 796–801
Barnum S R 1991 C4b-binding protein, a regulatory protein of complement;Immunol. Res. 10 28–42
Blom A M, Webb J, Villoutreix B O and Dahlback B 1999 A cluster of positively charged amino-acids in the C4BP α-chain is crucial for C4b binding and factor I cofactor function;J. Biol. Chem. 274 19237–19245
Daly J and Kotwal G J 1998 Pro-inflammatory complement activation by the Aβ peptide of Alzheimer’s disease is biologically significant and can be blocked by vaccinia virus complement control protein;Neurobiol. Aging 19 619–627
Earl P L and Moss B 1989 Vaccinia virus; inGenetics maps (ed.) S J O’Brian (New York: Cold Spring Harbor Lab), 5th edition, pp 1138–1148
Frank M M and Fries L F 1989 Complement; inFundamental immunology (ed.) W E Paul (New York: Raven) pp 679–701
Haig D M 2001 Subversion and piracy: DNA viruses and immune evasion;Res. Vet. Sci. 70 205–219
Holers V M, Cole J L, Lubin D M, Seya T and Atkinson J P 1985 Human C3b- and C4b-regulatory proteins: a new multigene family;Immunol. Today 6 188–192
Issacs S N, Kotwal G J and Moss B 1992 Vaccinia virus complement-control protein prevents antibody-dependant complement-enhanced neutralization of infectivity and contributes to virulence;Proc. Natl. Acad. Sci. USA 89 628–632
Keeling K L, Hicks R R, Mahesh J, Billings B B and Kotwal G J 2000 Local neutrophil influx following lateral fluid-percussion brain injury in rats is associated with accumulation of complement activation fragments of the third component (C3) of the complement system;J. Neuroimmunol. 105 20–30
Kirkitadze M D, Henderson C, Price N C, Kelly S M, Mullin N P, Parkinson J, Dryden D T F and Barlow P N 1999 Central modules of the vaccinia virus complement control protein are not in extensive contact;Biochem. J. 344 167–175
Kotwal G J and Moss B 1988 Vaccinia virus encodes a secretory polypeptide structurally related to complement control proteins;Nature (London)335 176–178
Kotwal G J and Moss B 1989 Vaccinia virus encodes two proteins that are structurally related to members of the plasma serine protease inhibitor superfamily;J. Virol. 63 600–696
Kotwal G J, Issacs S N and McKenzie R 1990 Vaccinia virus major secretory protein inhibits the classical complement cascade;Science 250 827
Krych M, Hauhart R and Atkinson J P 1998 Structure function analysis of the active sites of complement receptor type I;J. Biol. Chem. 273 8623–8629
Lalani A S and McFadden G 1997 Secreted poxvirus chemokine binding proteins;J. Leukoc Biol. 62 570–576
Lalani A S, Barrett J W and McFadden I 2000 Modulating chemokines: more lessons from viruses;Immunol. Today 21 100–106
Mahesh J, Daly J, Cheadle W G and Kotwal G J 1999 Elucidation of the early events contributing to zymosan-induced multiple organ dysfunction syndrome using MIP-1 alpha, C3 knockout, and C5-deficient mice;Shock 12 340–349
McKenzie R, Kotwal G J and Moss B 1992 Regulation of complement activity by vaccinia virus complement control protein;J. Infect. Dis. 166 1245
Moss B 1996 Poxviridae: The viruses and their replication; inFields virology (ed.) B N Fields (Lippincott: Raven) vol. 2, pp 2637–2671
Mossman K, Upton C, Buller R M and McFadden G 1995 Species specificity of ectromelia virus and vaccinia virus interferon-y binding proteins;Virology 208 762–769
Muller-Eberhard H J 1988 Molecular organization and function of the complement system;Annu. Rev. Biochem. 57 321–347
Murthy K H M, Smith S A, Ganesh V K, Judge K W, Mullin N, Barlow P N, Ogata C M and Kotwal G J 2001 Crystal structure of a complement control protein that regulates both pathways of complement activation and binds heparan sulfate proteoglycans;Cell 104 301–311
Nash P, Barrett J, Cao J X, Hota-Mitchell S, Lalani A S, Everett H, Xu X M, Robichaud J, Hnatiuk S, Ainslie C, Seet B T and McFadden G 1999 Immunomodulation by viruses: the myxoma virus story;Immunol. Rev. 168 103–120
Prodinger W M, Scwendinger M G, Schoch J, Kochle M, Harcher C C and Dierich M P 1998 Characterization of C3dg binding to a recess formed between consensus repeats 1 and 2 of complement receptor type 2;J. Immunol. 161 4604–4610
Reid K B M 1995 The complement system: A major effector mechanism in humoral immunity;Immunologist 3 206–211
Reynolds D N, Keeling K L, Molestina R, Srisatjaluk R, Butterfield J H, Ehringer W, Justus D E and Kotwal G J 2000 heparin binding activity of vaccinia virus complement control protein confers additional properties of uptake by mast cells and attachment to endothelial cells; inAdvances in animal virology (ed.) S Jameel (Villarreal: Science Publishers) pp 337–342
Senkevich T G, Bugert J J, Sisler J R, Koonin E V, Darai G and Moss B 1996 Genome sequence of human tumorigenic poxvirus: prediction of specific host response-evasion genes;Science 273 813–816
Smith S A, Mullin N P, Parkinson J, Shchelkunov S N, Totmenin A V, Loparev V N, Srisatjaluk R, Reynolds D N, Keeling K L, Justus D E, Barlow P N and Kotwal G J 2000 Conserved surface-exposed K/R-X-K/R motifs and net positive charge on poxvirus complement control proteins serve as putative heparin-binding sites and contribute to inhibition of molecular interactions with human endothelial cells: a novel mechanism for evasion of host defense;J. Virol. 74 5659–5666
Smith G L, Symons J A, Khanna A, Vanderplasschen A and Alcami A 1997 Vaccinia virus immune evasion;Immunol. Rev. 159 137–154
Soames C J, Day A J and Sim R B 1996 Prediction from sequence comparisons of residues of factor H involved in the interaction with complement component C3b;Biochem. J. 315 523–531
Tortorella D, Gewurz B E, Furman M H, Schust, D J and Ploegh H L 2000 Viral Subversion of the Immune System;Annu. Rev. Immunol. 18 861–926
Wiles A P, Shaw G, Bright J, Percelez A, Campbell L D and Barlow P N 1997 NMR studies of a viral protein that mimics the regulators of complement activation;J. Mol. Biol. 272 253–265
Yan S D, Fu J, Soto C, Chen X, Zhu H, Al-Mohanna F, Collison K, Zhu A, Stern E, Saido T, Tohyama, M, Ogawa, S, Roher A and Stern D 1997 An intracellular protein that binds amyloid-beta peptide and mediates neurotoxicity in Alzheimer’s disease;Nature (London)389 689–695
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Jha, P., Kotwal, G.J. Vaccinia complement control protein: Multi-functional protein and a potential wonder drug. J. Biosci. 28, 265–271 (2003). https://doi.org/10.1007/BF02970146
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF02970146