Herpes simplex virus glycoprotein C: molecular mimicry of complement regulatory proteins by a viral protein.
Herpes simplex virus (HSV) encodes a protein, glycoprotein C (gC), which binds to the third complement component, the central mediator of complement activation. In this study the structural and functional relationships of gC from HSV type 1 (HSV-1) and known human complement regulatory proteins factor H, properdin, factor B, complement receptor 1 (CR1) and 2 (CR2) were investigated. The interaction of gC with C3b was studied using purified complement components, synthetic peptides, antisera against different C3 fragments and anti-C3 monoclonal antibodies (mAb) with known inhibitory effects on C3-ligand interactions. All the mAb that inhibited gC/C3b interactions, in a differential manner, also prevented binding of C3 fragments to factors H, B, CR1 or CR2. No blocking was observed with synthetic peptides representing different C3 regions or with factor B and C3d, whereas C3b, C3c and factor H were inhibitory, as well as purified gC. There was no binding of gC to cobra venom factor (CVF), a C3c-like fragment derived from cobra gland. Purified gC bound to iC3, iC3b and C3c, but failed to bind to C3d. Glycoprotein C bound only weakly to iC3 derived from bovine and porcine plasma, thus indicating a preference of the viral protein for the appropriate host. Binding of gC was also observed to proteolytic C3 fragments, especially to the beta-chain, thus suggesting the importance of the C3 region as a binding site. Purified gC from HSV-1, but not HSV-2, inhibited the binding of factor H and properdin but not of CR1 to C3b. The binding of iC3b to CR2, a molecule involved in B-cell activation and binding of the Epstein-Barr virus, was also inhibited by the HSV-1 protein. As factor H and properdin, the binding of which was inhibited by gC, are important regulators of the alternative complement pathway, these data further support a role of gC in the evasion of HSV from a major first-line host defence mechanism, i.e. the complement system. In addition, the inhibition of the C3/CR2 interaction may suggest a possible immunoregulatory role of HSV glycoprotein C.
Huemer
H P
HP
Institute for Hygiene, University of Innsbruck, Austria.
Wang
Y
Y
Garred
P
P
Koistinen
V
V
Oppermann
S
S
D000911:Antibodies, Monoclonal / Q000276:immunology; D001665:Binding Sites; D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D003167:Complement Activation / Q000276:immunology; D003176:Complement C3 / Q000276:immunology*; D011415:Complement Factor B / Q000276:immunology; D017242:Complement Factor H / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D008024:Ligands; D011414:Properdin / Q000276:immunology; D011863:Radioimmunoassay; D017463:Receptors, Complement 3b / Q000276:immunology; D017464:Receptors, Complement 3d / Q000276:immunology; D018139:Simplexvirus / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; C493495:CFH protein, human; D003176:Complement C3; D008024:Ligands; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C038535:glycoprotein gC, herpes simplex virus type 1; D011414:Properdin; D017242:Complement Factor H; D011415:Complement Factor B