Herpes simplex virus glycoprotein E-glycoprotein I heterodimer (gE/gI)

The Herpes simplex virus (HSV) glycoprotein E (gE) and glycoprotein I (gI) form a non-covalent heterodimer on the viral envelope and the surface of infected cells. This complex functions as a viral Fc receptor (vFcR), which binds the Fc domain of host immunoglobulin G (IgG) with high affinity, effectively coating the virus in host antibodies in a bipolar fashion (Nagashunmugam et al., 1998, PubMed). By binding the Fc region, the gE/gI complex prevents host IgG from interacting with cellular Fc receptors on natural killer cells and neutrophils, thereby inhibiting antibody-dependent cellular cytotoxicity (ADCC) and complement activation (Chiu et al., 2022, PubMed). Additionally, the gE/gI heterodimer is essential for the efficient cell-to-cell spread of the virus, particularly in epithelial and neuronal tissues (Johnson et al., 1988, PubMed). Because of its critical role in both immune evasion and viral dissemination, the gE/gI complex is a major target for neutralizing monoclonal antibodies like UB-621 and next-generation vaccines. Blocking the interaction between gE/gI and the IgG Fc region restores the host's ability to clear the infection through standard immunological pathways.

Other names

Viral Fc receptorvFcRHSV gE/gI complexGlycoprotein E/Glycoprotein I complexHSV-1 gE/gIHSV-2 gE/gI

Therapeutic antibodies or vaccine-induced antibodies bind to the gE/gI heterodimer to block its viral Fc receptor (vFcR) activity, preventing the virus from binding the Fc region of host IgG and thereby restoring host immune effector functions like ADCC.