Influence of glycosylation and oligomerization of vaccinia virus complement control protein on level and pattern of functional activity and immunogenicity.
10.1007/s13238-010-0139-2
- Author:
Girish J KOTWAL
1
Author Information
1. Department of Pharmaceutical Sciences, Sullivan University College of Pharmacy, Louisville, KY, USA. Gkotwal@sullivan.edu
- Publication Type:Journal Article
- MeSH:
Amino Acid Sequence;
Animals;
Cell Line;
Cercopithecus aethiops;
Complement Activation;
drug effects;
immunology;
Complement System Proteins;
metabolism;
Dimerization;
Gene Expression;
Glycosylation;
Humans;
Molecular Sequence Data;
Protein Binding;
Protein Structure, Tertiary;
Recombinant Proteins;
genetics;
metabolism;
Smallpox;
immunology;
metabolism;
Structure-Activity Relationship;
Vaccinia virus;
chemistry;
immunology;
metabolism;
Variola virus;
chemistry;
immunology;
metabolism;
Viral Proteins;
genetics;
metabolism;
pharmacology
- From:
Protein & Cell
2010;1(12):1084-1092
- CountryChina
- Language:English
-
Abstract:
Vaccinia virus complement control protein (VCP) is one of the proteins encoded by vaccinia virus to modulate the host inflammatory response. VCP modulates the inflammatory response and protects viral habitat by inhibiting the classical and the alternative pathways of complement activation. The extended structure of VCP, mobility between its sequential domains, charge distribution and type of residues at the binding regions are factors that have been identified to influence its ability to bind to complement proteins. We report that a Lister strain of vaccinia virus encodes a VCP homolog (Lis VCP) that is functional, glycosylated, has two amino acids less than the well-characterized VCP from vaccinia virus WR strain (WR VCP), and the human smallpox inhibitor of complement enzymes (SPICE) from variola virus. The glycosylated VCP of Lister is immunogenic in contrast to the weak immunogenicity of the nonglycosylated VCP. Lis VCP is the only orthopoxviral VCP homolog found to be glycosylated, and we speculate that glycosylation influences its pattern of complement inhibition. We also correlate dimerization of VCP observed only in mammalian and baculovirus expression systems to higher levels of activity than monomers, observed in the yeast expression system.
