title: Murine gammaherpesvirus-68 glycoprotein H-glycoprotein L complex is a major target for neutralizing monoclonal antibodies.
abstract: Herpesviruses characteristically persist in immune hosts as latent genomes, but to transmit infection they must reactivate and replicate lytically. The interaction between newly formed virions and pre-existing antibody is therefore likely to be a crucial determinant of viral fitness. Murine gammaherpesvirus-68 (MHV-68) behaves as a natural pathogen of conventional, inbred mice and consequently allows such interactions to be analysed experimentally in a relatively realistic setting. Here, monoclonal antibodies (mAbs) were derived from MHV-68-infected mice and all those recognizing infected-cell surfaces were tested for their capacity to neutralize MHV-68 virions. All of the neutralizing mAbs identified were specific for the viral glycoprotein H (gH)-gL heterodimer and required both gH and gL to reproduce their cognate epitopes. Based on antibody interference, there appeared to be two major neutralization epitopes on gH-gL. Analysis of a representative mAb indicated that it blocked infection at a post-binding step--either virion endocytosis or membrane fusion.
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Gill
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: Laurent
authors.initials: L
authors.lastname: Gillet
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: Susanna
authors.initials: S
authors.lastname: Colaco
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: Janet S
authors.initials: JS
authors.lastname: May
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: Brigitte D
authors.initials: BD
authors.lastname: de Lima
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: Philip G
authors.initials: PG
authors.lastname: Stevenson
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D000918:Antibody Specificity; D002460:Cell Line; D006224:Cricetinae; D000939:Epitopes / Q000276:immunology; D006566:Herpesviridae Infections / Q000276:immunology / Q000821:virology; D051379:Mice; D009500:Neutralization Tests; D018144:Rhadinovirus / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D014412:Tumor Virus Infections / Q000276:immunology / Q000821:virology; D014759:Viral Envelope Proteins / Q000276:immunology*; D014771:Virion / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000939:Epitopes; D014759:Viral Envelope Proteins