Monoclonal antibodies against three major glycoproteins of varicella-zoster virus.
Varicella-zoster virus (VZV) codes for three prominent glycoproteins--gp62, gp98, and gp118--in infected cell cultures. To characterize individually these known immunogens, we first inoculated BALB/c mice with crude VZV extracts, produced hybridoma cultures by Köhler-Milstein cell-fusion technology, and screened culture supernatants by indirect immunofluorescence for reactivity directed against unfixed VZV-infected cells (FAMA assay). Supernatants from five independently derived and subcloned hybridomas with a high VZV-FAMA titer but no reactivity against either uninfected or herpes simplex virus-infected cells were further analyzed by immunoprecipitation of [3H]fucose-labeled and detergent-solubilized VZV antigen preparations. Fractionation of the precipitates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated that four monoclonal antibodies reacted with both gp62 and gp98, and one precipitated only gp118. The profiles were unchanged whether performed under reducing or nonreducing conditions. When assayed for neutralizing activity, the secretory product of the single anti-gp118 hybridoma, but not the supernatants from the four anti-gp62/gp98 clones, inhibited VZV plaque formation by greater than 80%. Thus, at least one of the glycosylated antigens detected by the FAMA assay is a determinant which elicits neutralizing activity.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis* / Q000096:biosynthesis / Q000276:immunology; D000914:Antibodies, Viral / Q000032:analysis / Q000096:biosynthesis; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions / Q000187:drug effects; D000956:Antigens, Viral / Q000008:administration & dosage / Q000276:immunology*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006168:Guinea Pigs; D006562:Herpes Zoster / Q000209:etiology / Q000276:immunology*; D014645:Herpesvirus 3, Human / Q000276:immunology; D006801:Humans; D008623:Mercaptoethanol / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D011817:Rabbits; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D014759:Viral Envelope Proteins; D014764:Viral Proteins; D012967:Sodium Dodecyl Sulfate; D008623:Mercaptoethanol