Herpes simplex virus type 1 glycoprotein B and C heparan sulfate-binding sites and host cell heparan sulfate proteoglycans (HSV-1 gB/gC-HSPG interaction)

The interaction between Herpes simplex virus type 1 (HSV-1) glycoproteins and host cell heparan sulfate proteoglycans (HSPGs) represents the initial and essential step of viral infection (Shukla & Spear, 2001, J. Clin. Invest.). HSV-1 utilizes its envelope glycoproteins, specifically glycoprotein C (gC) and glycoprotein B (gB), to bind to the negatively charged sulfate groups of heparan sulfate chains on the host cell surface (Karasneh & Shukla, 2011, Methods Mol. Biol.). This attachment serves to concentrate the virus on the cell membrane, facilitating subsequent interactions with specific entry receptors like nectin-1 or herpesvirus entry mediator (HVEM). Because this interaction is a prerequisite for viral entry and subsequent replication, it is a major target for the development of entry inhibitors and microbicides. Therapeutic agents such as heparan sulfate mimetics or polyanionic compounds act as decoys, binding to the viral glycoproteins and preventing them from docking onto the host cell (UniProt P06437, P06473). While effective in reducing viral infectivity, drug development must account for potential interference with endogenous HSPG roles in blood coagulation and cellular signaling.

Other names

HSV-1 attachment receptorsgB-HSPG complexgC-HSPG complexHeparan sulfate proteoglycansHSPGHSV-1 gB and gC binding sites

Competitive inhibition of viral attachment to host cells by mimicking heparan sulfate or blocking the binding sites on viral glycoproteins gB and gC.