Herpes Simplex Virus 1 Envelope Glycoprotein C Shields Glycoprotein D to Protect Virions from Entry-Blocking Antibodies

bioRxiv [Preprint]. 2024 Aug 20:2024.08.20.608756. doi: 10.1101/2024.08.20.608756.

Abstract

Herpes simplex virus 1 (HSV-1) gD interaction with the host cell receptor nectin-1 triggers the membrane fusion cascade during viral entry. Potent neutralizing antibodies to gD prevent receptor-binding or prevent gD interaction with gH/gL critical for fusion. HSV has many strategies to evade host immune responses. We investigated the ability of virion envelope gC to protect envelope gD from antibody neutralization. HSV-1 lacking gC was more sensitive to neutralization by anti-gD monoclonal antibodies than a wild type rescuant virus. gD in the HSV-1 gC-null viral envelope had enhanced reactivity to anti-gD antibodies compared to wild type. HSV-1 ΔgC binding to the nectin-1 receptor was more readily inhibited by a neutralizing anti-gD monoclonal antibody. HSV-1 ΔgC was also more sensitive to inhibition by soluble nectin-1 receptor. The viral membrane protein composition of HSV-1 ΔgC was equivalent to that of wild type, suggesting that the lack of gC is responsible for the increased reactivity of gD-specific antibodies and the consequent increased susceptibility to neutralization by those antibodies. Together, the results suggest that gC in the HSV-1 envelope shields both receptor-binding domains and gH/gL-interacting domains of gD from neutralizing antibodies, facilitating HSV cell entry.

Publication types

  • Preprint