Herpes simplex virus type 2 envelope glycoproteins (HSV-2 glycoproteins)

Herpes simplex virus type 2 (HSV-2) envelope glycoproteins are a group of essential proteins, including gB, gC, gD, gH, and gL, that facilitate viral entry and immune evasion. These proteins are embedded in the viral envelope and coordinate the complex process of attaching to host cell receptors and fusing the viral and host membranes (UniProt: P06476). Specifically, gD binds to host receptors like HVEM or Nectin-1, triggering a cascade involving the gH/gL complex that ultimately activates the fusion protein gB (PubMed: 25631007). Additionally, glycoproteins like gC and the gE/gI complex play significant roles in immune evasion by inhibiting the complement activation and interfering with antibody-mediated responses. As the primary targets for neutralizing antibodies, these glycoproteins are the focus of various therapeutic interventions, including monoclonal antibodies like UB-621 and subunit vaccines like GEN-003, which aim to reduce viral shedding and clinical recurrences (ClinicalTrials.gov: NCT04714060). Despite their promise, the latent nature of HSV-2 infection remains a significant hurdle for therapies targeting these surface proteins.

Other names

HSV-2 surface proteinsHSV-2 envelope proteinsGlycoprotein B (gB)Glycoprotein D (gD)Glycoprotein H (gH)Glycoprotein L (gL)gB2gD2gH2gL2

The primary mechanism of action for drugs targeting HSV-2 envelope glycoproteins involves the neutralization of viral particles to prevent host cell attachment and membrane fusion. Monoclonal antibodies typically bind to specific epitopes on glycoproteins like gD or gB, sterically hindering their interaction with host receptors such as HVEM or Nectin-1, or preventing the conformational changes required for fusion (PubMed: 30104355). Vaccines targeting these glycoproteins aim to induce high titers of neutralizing antibodies and activate T-cell responses to reduce viral shedding and lesion frequency (PubMed: 28111307).