Glycoprotein C of herpes simplex virus 1 is an inhibitor of the complement cascade.
Mammalian cells in culture express membrane receptors for C3b when infected with HSV-1. C3b binding is mediated by glycoprotein C (gC), a virus-specified membrane glycoprotein. In view of the inhibitory functions of other C3b-binding proteins, we studied the capacity of gC to modulate complement activation. Glycoprotein C was purified from HSV-1-infected cells by immunoaffinity chromatography. Glycoprotein C, but not a control viral glycoprotein, demonstrated dose-dependent acceleration of decay of C3bBb sites. In addition, gC produced a dose-dependent, time-independent depression of the overall hemolytic efficiency of C3bBb sites. Inhibition of C5b6-initiated reactive lysis of cells bearing C3b, but not cells bearing antibody alone, by gC suggests that the second effect represents interference with the C3b-C5/5b interaction. This hypothesis is supported by the failure of gC to inhibit reactive lysis when added after C5b67 insertion into target cells. Glycoprotein C does not accelerate C14b2a decay, nor does it impair classical pathway hemolytic efficiency when excess C5 is present. By limiting available C5/5b, some gC inhibition of C3b-C5/5b interactions can be unmasked in the classical pathway system. Glycoprotein C is devoid of factor I co-factor activity. HSV-1 gC is a modulator of complement activation, especially via the alternative pathway, and may represent a novel viral mechanism for evading host defense processes.
D000818:Animals; D003166:Complement Activating Enzymes / Q000037:antagonists & inhibitors*; D003167:Complement Activation / Q000187:drug effects*; D050577:Complement C3-C5 Convertases / Q000037:antagonists & inhibitors*; D017244:Complement Factor I; D003170:Complement Pathway, Alternative / Q000187:drug effects*; D003165:Complement System Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D010450:Endopeptidases / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D018139:Simplexvirus / Q000502:physiology; D014759:Viral Envelope Proteins / Q000494:pharmacology*
D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1; C038535:glycoprotein gC, herpes simplex virus type 1; D003165:Complement System Proteins; D003166:Complement Activating Enzymes; D010450:Endopeptidases; D050577:Complement C3-C5 Convertases; D017244:Complement Factor I