Antibody evasion by the N terminus of murid herpesvirus-4 glycoprotein B.
Herpesviruses characteristically transmit infection from immune hosts. Although their success in escaping neutralization by pre-formed antibody is indisputable, the underlying molecular mechanisms remain largely unknown. Glycoprotein B (gB) is the most conserved component of the herpesvirus entry machinery and its N terminus (gB-NT) is a common neutralization target. We used murid herpesvirus-4 to determine how gB-NT contributes to the virus-antibody interaction. Deleting gB-NT had no obvious impact on virus replication, but paradoxically increased virion neutralization by immune sera. This reflected greater antibody access to neutralization epitopes on gH/gL, with which gB was associated. gB-NT itself was variably protected against antibody by O-linked glycans; on virions from epithelial cells it was protected almost completely. gB-NT therefore provides a protective and largely protected cover for a vulnerable part of gH/gL. The conservation of predicted glycosylation sites in other mammalian herpesvirus gB-NTs suggests that this evasion mechanism is widespread. Interestingly, the gB-NT glycans that blocked antibody binding could be targeted for neutralization instead by a lectin, suggesting a means of therapeutic counterattack.
Gillet
Laurent
L
Division of Virology, Department of Pathology, University of Cambridge, Cambridge, UK.
Stevenson
Philip G
PG
D000276:Adjuvants, Immunologic / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D016525:Antigenic Modulation; D002460:Cell Line; D005260:Female; D016679:Genome, Viral; D006566:Herpesviridae Infections / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D009500:Neutralization Tests; D037121:Plant Lectins / Q000378:metabolism; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism; D018144:Rhadinovirus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D014771:Virion / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D037121:Plant Lectins; D011134:Polysaccharides; D014759:Viral Envelope Proteins; C043696:jacalin