Dual impacts of a glycan shield on the envelope glycoprotein B of HSV-1: evasion from human antibodies in vivo and neurovirulence

Abstract

Identificationof the mechanisms of viral evasion from human antibodies is crucial both for understanding viral pathogenesis and for designing effectivevaccines. Here we show in cell cultures that an N-glycan shield on the herpes simplex virus 1 (HSV-1) envelope glycoprotein B (gB) mediated evasion from neutralization and antibody-dependent cellular cytotoxicity due to pooled γ-globulins derived from human blood. We also demonstrated that the presence of human γ-globulins in mice and immunity to HSV-1 induced by viral infection in mice significantlyreduced replication in their eyes of a mutant virus lacking the glycosylation site but had little effecton the replication of its repaired virus. These results suggest that an N-glycan shield on a specificsite of HSV-1 envelope gB mediated evasion from human antibodies in vivo and from HSV-1 immunity induced by viral infection in vivo. Notably, we also found that an N-glycan shield on a specificsite of HSV-1 gB was significantfor HSV-1 neurovirulence and replication in the central nervous system of naïve mice. Thus, we have identifieda critical N-glycan shield on HSV-1 gB that has dual impacts, namely evasion from human antibodies in vivo and viral neurovirulence.