title: Variability of herpes simplex virus 1 gL and anti-gL antibodies that inhibit cell fusion but not viral infectivity.
abstract: Herpes simplex virus type 1 gL lacks a transmembrane domain but stably associates with membranes through its oligomerization with the integral membrane glycoprotein designated gH. The gH-gL oligomers are essential for virion infectivity and virus-induced cell fusion. Monoclonal and polyclonal antibodies were raised against HSV-1(KOS) gL as probes for antigenic structure and functional protein domains. Antigenic determinants recognized by these antibodies were found to be present on gL expressed by many, but not all, strains of HSV-1 and were not detected on gL expressed by HSV-2 strains. These antigenic determinants were localized to the C-terminal region of HSV-1 gL, where amino acid substitutions define at least two classes of HSV-1 gL and where the sequences of HSV-1 and HSV-2 gL diverge considerably. The antibodies were extremely effective at inhibiting virus-induced cell fusion, provided the virus strain expressed the relevant antigenic determinants, but failed to neutralize viral infectivity despite demonstrable binding to virions. These results define strain-dependent differences in the structure and antigenic conformation of HSV-1 forms of gL and suggest that the roles of gL in cell fusion and viral entry are different.
authors.affiliation: Microbiology-Immunology Department, Northwestern University Medical School, Chicago, Illinois 60611, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Novotny
authors.forename: M L
authors.initials: ML
authors.lastname: Parish
authors.forename: P G
authors.initials: PG
authors.lastname: Spear
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D000940:Antigenic Variation; D000956:Antigens, Viral / Q000276:immunology; D001483:Base Sequence; D002522:Chlorocebus aethiops; D017931:DNA Primers; D018259:Herpesvirus 1, Human / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D008561:Membrane Fusion; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011817:Rabbits; D014407:Tumor Cells, Cultured; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D017931:DNA Primers; D014759:Viral Envelope Proteins; C077407:glycoprotein L, Human herpesvirus 1