title: Herpes simplex virus glycoproteins gC-1 and gC-2 bind to the third component of complement and provide protection against complement-mediated neutralization of viral infectivity.
abstract: Cells infected with herpes simplex virus type 1 (HSV-1) form rosettes with C3b-coated erythrocytes, whereas cells infected with herpes simplex virus type 2 (HSV-2) or other herpes viruses do not. It was reported that glycoprotein C of HSV-1 (gC-1) mediates the binding of C3b-coated erythrocytes to infected cells and has regulatory (decay-accelerating) activity for the alternative pathway C3 convertase of human complement. We show here that solubilized gC-1 binds to iC3-Sepharose affinity columns. We also report that solubilized gC-2, the genetically related glycoprotein specified by HSV-2, binds to iC3-Sepharose. mAb specific for gC-1 or gC-2 and mutant viral strains were used to identify the C3-binding glycoproteins. In other experiments, HSV-1 mutant strains and recombinants, differing only in their expression of gC, were tested for sensitivity to neutralization by human complement in the presence or absence of antibodies specific for HSV gD. In either case the gC- strain was most sensitive. Expression of gC-1 or gC-2 by isogenic insertion mutants provided protection against complement-mediated neutralization. These results indicate that the genetically and structurally related gC-1 and gC-2 share the functional activity of binding to human C3 and enhance viral infectivity.
authors.affiliation: Howard Hughes Medical Institute Laboratories, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: T A
authors.initials: TA
authors.lastname: McNearney
authors.forename: C
authors.initials: C
authors.lastname: Odell
authors.forename: V M
authors.initials: VM
authors.lastname: Holers
authors.forename: P G
authors.initials: PG
authors.lastname: Spear
authors.forename: J P
authors.initials: JP
authors.lastname: Atkinson
mesh_terms: D002846:Chromatography, Affinity; D003176:Complement C3 / Q000276:immunology*; D006801:Humans; D018139:Simplexvirus / Q000276:immunology* / Q000472:pathogenicity; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D003176:Complement C3; D014759:Viral Envelope Proteins; C048232:glycoprotein C, herpes simplex virus type 2; C038535:glycoprotein gC, herpes simplex virus type 1