Herpesvirus glycoprotein B

The herpesvirus glycoprotein B is a type-1 transmembrane protein with a signal sequence at its N terminus.[2] The crystal structure of herpes simplex virus (HSV) type-1 and Epstein–Barr virus glycoprotein B ectodomains were solved as a trimer, revealing five structural domains (I-V).[3][4] Domain I contains two internal fusion loops, thought to insert into the cellular membrane during virus-cell fusion.[5] In HSV, domain II is hypothesized to interact with another herpesvirus glycoprotein, gH/gL, during the fusion process.[6] Domain III consists of a structurally important elongated alpha helix, while domain IV is hypothesized to interact with cellular receptors.[7] Finally, domain V acts in conjunction with domain I during protein-lipid interactions. In HSV, neutralizing monoclonal antibodies map to structural domains I, II, IV and V.[7] Due to its unique structure, herpesvirus glycoprotein B (along with vesicular stomatitis virus glycoprotein G and baculovirus gp64) belongs to a new class of viral membrane fusion glycoproteins, class III.[3]

The herpesvirus glycoprotein B is the most highly conserved of all surface glycoproteins and acts primarily as a fusion protein. The precise functions of gB and gH/gL are unknown but they are required for viral entry into the cell and constitute the core fusion machinery. The claim that gB is involved in fusion comes from the notable syncytial phenotype caused by certain mutations within the cytoplasmic domain of glycoprotein B,[8] as well as its structural homology to other viral fusion proteins.[3]