Influence of glycosylation and oligomerization of vaccinia virus complement control protein on level and pattern of functional activity and immunogenicity

Protein Cell. 2010 Dec;1(12):1084-92. doi: 10.1007/s13238-010-0139-2. Epub 2011 Jan 8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Chlorocebus aethiops
  • Complement Activation / drug effects
  • Complement Activation / immunology
  • Complement System Proteins / metabolism
  • Dimerization
  • Gene Expression
  • Glycosylation
  • Humans
  • Molecular Sequence Data
  • Protein Binding
  • Protein Structure, Tertiary
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism*
  • Smallpox / immunology
  • Smallpox / metabolism
  • Structure-Activity Relationship
  • Vaccinia virus / chemistry
  • Vaccinia virus / immunology*
  • Vaccinia virus / metabolism*
  • Variola virus / chemistry
  • Variola virus / immunology
  • Variola virus / metabolism
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*
  • Viral Proteins / pharmacology

Substances

  • Recombinant Proteins
  • Viral Proteins
  • complement-control protein, Vaccinia virus
  • Complement System Proteins