Herpes simplex virus type 2 envelope glycoproteins (gB, gD, gH, gL) (HSV-2 glycoproteins)

The Herpes simplex virus type 2 (HSV-2) envelope glycoproteins, specifically gB, gD, gH, and gL, constitute the essential machinery for viral entry and the virus–host cell surface interface (NIH, 2021). This complex process begins with viral attachment to host cell heparan sulfate proteoglycans via gC and gB, followed by the high-affinity binding of gD to specific receptors such as Herpesvirus Entry Mediator (HVEM) or Nectin-1 (NIH, 2025). This binding triggers a conformational change in the gH/gL heterodimer, which in turn activates gB, the primary fusogen, to mediate the fusion of the viral envelope with the host cell membrane (NIH, 2021). Beyond entry, these glycoproteins are critical for cell-to-cell spread and play roles in evading the host immune response through mechanisms like glycan shielding (NIH, 2014). Therapeutically, these glycoproteins are prime targets for the development of entry inhibitors, including monoclonal antibodies like HDIT101, which targets gB (NIH, 2022), and UB-621, which targets gD (United BioPharma, 2021). While traditional nucleoside analogs target viral DNA replication, targeting the entry interface offers a strategy to treat acyclovir-resistant strains and reduce viral shedding (NIH, 2025). Challenges in this field include the high degree of redundancy in receptor usage and the need for robust Fc-mediated effector functions to achieve clinical efficacy (BioRxiv, 2025).

Other names

HSV-2 entry glycoproteinsHSV-2 fusion machineryHSV-2 surface glycoproteinsGlycoprotein B (gB)Glycoprotein D (gD)Glycoprotein H (gH)Glycoprotein L (gL)HSV-2 entry complex

Inhibition of viral entry by blocking attachment or membrane fusion, neutralization of cell-free virus, and inhibition of cell-to-cell spread.