Antibody evasion by the N terminus of murid herpesvirus-4 glycoprotein B

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Abstract
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.