title: Herpes simplex virus type 1 glycoprotein gC mediates immune evasion in vivo.
abstract: Many microorganisms encode proteins that interact with molecules involved in host immunity; however, few of these molecules have been proven to promote immune evasion in vivo. Herpes simplex virus type 1 (HSV-1) glycoprotein C (gC) binds complement component C3 and inhibits complement-mediated virus neutralization and lysis of infected cells in vitro. To investigate the importance of the interaction between gC and C3 in vivo, we studied the virulence of a gC-null strain in complement-intact and C3-deficient animals. Using a vaginal infection model in complement-intact guinea pigs, we showed that gC-null virus grows to lower titers and produces less severe vaginitis than wild-type or gC rescued virus, indicating a role for gC in virulence. To determine the importance of complement, studies were performed with C3-deficient guinea pigs; the results demonstrated significant increases in vaginal titers of gC-null virus, while wild-type and gC rescued viruses showed nonsignificant changes in titers. Similar findings were observed for mice where gC null virus produced significantly less disease than gC rescued virus at the skin inoculation site. Proof that C3 is important was provided by studies of C3 knockout mice, where disease scores of gC-null virus were significantly higher than in complement-intact mice. The results indicate that gC-null virus is approximately 100-fold (2 log10) less virulent that wild-type virus in animals and that gC-C3 interactions are involved in pathogenesis.
authors.affiliation: Departments of Medicine, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Lubinski
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: A M
authors.initials: AM
authors.lastname: Soulika
authors.forename: R
authors.initials: R
authors.lastname: Burger
authors.forename: R A
authors.initials: RA
authors.lastname: Wetsel
authors.forename: H
authors.initials: H
authors.lastname: Colten
authors.forename: G H
authors.initials: GH
authors.lastname: Cohen
authors.forename: R J
authors.initials: RJ
authors.lastname: Eisenberg
authors.forename: J D
authors.initials: JD
authors.lastname: Lambris
authors.forename: H M
authors.initials: HM
authors.lastname: Friedman
mesh_terms: D000818:Animals; D002459:Cell Fusion; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003176:Complement C3 / Q000235:genetics / Q000378:metabolism; D004285:Dogs; D006168:Guinea Pigs; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D010641:Phenotype; D018139:Simplexvirus / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000502:physiology*; D014774:Virulence / Q000502:physiology
chemical_list: D003176:Complement C3; D014759:Viral Envelope Proteins; C038535:glycoprotein gC, herpes simplex virus type 1