The role of herpes simplex virus glycoproteins in the virus replication cycle.

At least nine of the eleven herpes simplex virus (HSV) glycoproteins so far known have been widely characterised as regards their role in the virus replication cycle. During early virus-to-cell adsorption ("adsorption"), glycoprotein C (gC) interacts with the glycosoaminoglycan (GAG) heparan sulphate (HS), located on the cell membrane surface. This interaction is labile until other glycoproteins such as B and D (gB and gD) begin to participate in the entry process. gB also harbours a site for interaction with GAGs, while gD provides a stabile attachment to cellular receptors ("receptors") such as the herpesvirus entry mediator (HVEM). Late adsorption is associated with a conformation change of gD occurring after the receptor binding, a step followed by interaction of gD with the gH/gL heterodimer (complex). Fusion domains of the gH/gL complex and gB enable the pH-independent virus-into-cell penetration ("penetration"). The gE/gI complex and gM interact with the receptors at cell junctions in order to facilitate cell-to-cell spread of the virus along the basolateral surface of polarised cells and/or a similar intercellular spread in nonpolarised cells by avoiding virion release, gK, the only so far known HSV-coded glycoprotein which is not incorporated into virions, plays an essential role in the virus capsid envelopment at the nuclear membrane and in the virion transport to the cell surface. Unusually large polykaryocytes arise due to mutations in syn (syncytium) loci of the viral genome, which were mapped to UL53 (syn1) and UL27 (syn3) genes coding for gK and gB, respectively, while the genes UL20 and UL24 (both syn5) code for nonglycosylated cell membrane-associated proteins ("membrane proteins"). The products of nonmutated syn genes either downregulate the fusion of plasma membranes of infected cells ("membrane fusion") or protect them from undesirable fusion events.