Glycoprotein H–Glycoprotein L complex (gH/gL)

The glycoprotein H–glycoprotein L complex (gH/gL) is a stable heterodimeric protein complex found on the surface of all herpesviruses, including herpes simplex virus (HSV), Epstein–Barr virus (EBV), human cytomegalovirus (HCMV), and human herpesvirus 7 (HHV-7), among others[1][2][3][4][5][7]. Both gH and gL are glycoproteins: gH is a transmembrane protein with a large ectodomain and a single transmembrane region, while gL lacks a transmembrane segment and acts as a scaffold for proper folding and trafficking of gH[1][2][3][4]. The gH/gL complex does not directly bind cell receptors or act as a viral fusogen; instead, it functions as a structural adapter that receives triggering signals from viral receptor-binding proteins and then activates gB, the primary fusion protein, to drive membrane fusion[1][3][5]. Crystal structures reveal extensive hydrophobic interfaces and specific domain contacts essential for stability and function[1][3][6]. The complex is highly conserved among herpesviruses and is a major target of the humoral immune response[7]. Disrupting gH/gL function impedes herpesvirus entry, making it an attractive — but still mostly preclinical — target for antivirals and vaccines[1][7].

Other names

Glycoprotein H–glycoprotein L heterodimergH–gLHerpesvirus fusion complex (less common)

Blockade of gH/gL interaction with gB (neutralization of infection by inhibiting formation of the fusion complex[1][7]); Inhibition of membrane fusion and viral entry (by disrupting gH/gL function[1][7])