Herpes simplex virus type 2 envelope glycoproteins and heparan sulfate-binding sites (HSV-2 glycoproteins/HS-binding sites)

Herpes simplex virus type 2 (HSV-2) utilizes a complex set of envelope glycoproteins, including gB, gC, gD, gH, and gL, to facilitate host cell entry and infection (Agelidis & Shukla, 2020, FEBS J). The infection process begins with the low-affinity attachment of viral glycoproteins gB and gC to heparan sulfate proteoglycans (HSPGs) on the host cell surface (Shukla & Spear, 2001, J Clin Invest). This initial tethering allows the virus to roll along the cell surface until glycoprotein gD binds to high-affinity entry receptors such as nectin-1 or herpesvirus entry mediator (HVEM) (Campadelli-Fiume et al., 2007, Rev Med Virol). These interactions trigger a conformational change that activates the core fusion machinery, consisting of the gH/gL complex and gB, leading to the fusion of the viral envelope with the host plasma membrane (UniProt, 2024). Because these glycoproteins and their binding sites are essential for viral infectivity, they are primary targets for the development of entry inhibitors and topical microbicides (Pirrone et al., 2011, Antiviral Res). Therapeutic strategies often involve polyanionic compounds that mimic heparan sulfate to block attachment or monoclonal antibodies that neutralize specific glycoproteins to prevent the establishment of latency (Cheshenko et al., 2004, J Biol Chem).

Other names

HSV-2 gB/gC/gD/gH/gL complexHSV-2 entry receptorsHeparan sulfate-binding glycoproteinsHSV-2 attachment proteinsHSV-2 fusion machinery

Inhibition of viral attachment by competing for heparan sulfate binding sites on the viral surface and blocking glycoprotein-mediated membrane fusion with the host cell membrane.