The interaction of glycoprotein C of herpes simplex virus types 1 and 2 with the alternative complement pathway

Virology. 1994 Sep;203(2):299-312. doi: 10.1006/viro.1994.1488.


Glycoprotein C (gC) of herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2) binds the human complement fragment C3b, but the two proteins differ in their ability to bind C3b on infected cell surfaces. In addition, gC-1, but not gC-2, accelerates the decay of the alternative pathway C3 convertase, thereby affecting later steps of the complement cascade. Previously, we constructed linker insertion and deletion mutants of gC-1 and gC-2 and used transient transfection to express mutant proteins in uninfected cells. In spite of the differences between gC-1 and gC-2, C3b binding was localized to residues within the central portion of both proteins, encompassing the first four cysteines. For gC-1, deletion mutants lacking amino acids 33 to 123 or 367 to 469 or lacking both regions still bound C3b. We recombined these deleted forms of gC-1 into gC-39, an HSV-1 strain lacking the gC gene. The altered forms of gC-1 were incorporated into virions, expressed on the surface of infected cells, and bound C3b. We used these proteins to investigate the structural basis for the inhibitory action of gC-1 on the complement cascade. We found that gC-1 does not inhibit formation of the alternative pathway C3 convertase. This convertase is stabilized by the serum protein properdin. Purified gC-1, but not gC-2, inhibits the binding of properdin to C3b, suggesting that this destabilizes the convertase. The mutant lacking amino acids 367 to 449 was able to inhibit properdin binding to a limited extent when present at high concentrations, although it bound to C3b more weakly than wild-type gC. In contrast, the protein lacking amino acids 33 to 123 was unable to inhibit properdin binding to C3b. Thus, gC-1 contains two structural domains, one for C3b binding, residues 124 to 366, and another, residues 33 to 133, which interferes with properdin binding to C3b.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Western
  • Complement C3 / metabolism
  • Complement Pathway, Alternative*
  • Enzyme-Linked Immunosorbent Assay
  • Mutation
  • Neutralization Tests
  • Properdin / metabolism
  • Receptors, Complement 3b / analysis
  • Recombinant Proteins / biosynthesis
  • Vero Cells
  • Viral Envelope Proteins / analysis
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / physiology*


  • Complement C3
  • Receptors, Complement 3b
  • Recombinant Proteins
  • Viral Envelope Proteins
  • glycoprotein C, herpes simplex virus type 2
  • glycoprotein gC, herpes simplex virus type 1
  • Properdin