IMMUNE EVASION PROPERTIES OF HERPES-SIMPLEX VIRUS TYPE-1 GLYCOPROTEINGC

Herpes simplex virus type 1 (HSV-1) glycoprotein gC binds complement c omponent C3b, and purified gC inhibits complement activation. Two HSV strains carrying mutations in the gC gene which rendered them unable t o bind C3b were compared with wild-type and marker-rescued viruses to evaluate the role of gC on the virion in protecting HSV-1 from complem ent-mediated neutralization. The gC mutant viruses were markedly susce ptible to neutralization by nonimmune human serum, showing up to a 5,0 00-fold decline in titer after 1 h of incubation with serum. Tn contra st, wild-type or marker-rescued viruses showed a twofold reduction in titer. Studies with hypogammaglobulinemic and immunoglobulin G-deplete d serum supported the observation that neutralization occurred in the absence of antibody. Neutralization of gC mutant strains by nonimmune serum was rapid; their half-life was 2 to 2.5 min, compared with 1 h f or wild-type virus. Ethylene glycol-bis(beta-aminoethyl ether)-N,N,N', N'-tetraacetic acid (EGTA)-treated human serum or C4-deficient guinea pig serum failed to neutralize gC mutant strains, indicating a role fo r components of the classical complement pathway. gC had little additi onal effect on neutralization by the combination of antibody plus comp lement compared with complement alone. The results indicate that the m agnitude of the protection offered by gC-1 is larger than previously r ecognized; that in the absence of gC-1, complement neutralization is r apid and is mediated by components of the classical complement pathway ; and that gC mainly protects against antibody-independent complement neutralization, suggesting a probable role for gC early in infection, before antibodies develop.