1.G.10 The Herpes Simplex Virus Membrane Fusion Complex (HSV-MFC) Family

Members of class III of viral fusion proteins share common structural features and molecular architecture, although they belong to evolutionary distant viruses and carry no sequence homology (Backovic and Jardetzky, 2011). Based of the experimentally determined three-dimensional structures of their ectodomains, glycoprotein B (gB) of herpesviruses, G protein of rhabdoviruses and glycoprotein 64 (gp64) of baculoviruses have been identified as class III fusion proteins. The structures are proposed to represent post-fusion conformations, and they reveal trimeric, elongated, rod-like molecules, with each protomer being composed of five domains. Sequences which interact with target membranes and form the fusion peptides are located in two loops found at one end of the molecule. Class III fusion proteins are embedded in the viral envelope with the principal function of catalyzing fusion of the viral and cellular membranes. G protein is the only class III fusion protein for which structures of both pre- and post-fusion states have been determined, shedding light on the mechanism involved in the conformational change and membrane fusion (Backovic and Jardetzky, 2011).

Herpes Simplex Virus-1 (HSV1) uses four viral surface glycoproteins (gB, gD, gH and gL) to effect membrane fusion. Following gD binding to one of its entry receptors, membrane fusion is mediated by gB and the heterodimer gH/gL (Reske et al., 2007). gHL counterparts are involved in the fusion process of all other members of the herpesvirus family (Browne, 2009).



Apellaniz B., Huarte N., Largo E. and Nieva JL. (2014). The three lives of viral fusion peptides. Chem Phys Lipids. 181:40-55.

Backovic, M. and T.S. Jardetzky. (2011). Class III viral membrane fusion proteins. Adv Exp Med Biol 714: 91-101.

Browne, H.M. (2009). The role of glycoprotein H in herpesvirus membrane fusion. Protein Pept Lett 16: 760-765.

Feng, D. and R. Jia. (2016). [Molecular Mechanism of Glycoprotein-induced Cell-Cell Fusion of Herpesviruses]. Bing Du Xue Bao 32: 101-107.

Reske, A., G. Pollara, C. Krummenacher, B.M. Chain, and D.R. Katz. (2007). Understanding HSV-1 entry glycoproteins. Rev Med Virol 17: 205-215.


TC#NameOrganismal TypeExample

The herpes envelope glycoprotein class III membrane fusion system including glycoproteins gB, gD, gH and gL.  There are two fusion peptides of 8 aas each that form a bipartite system (Apellániz et al. 2014; Feng and Jia 2016).

Viruses (Herpesviridae)

Class III fusion system of human herpes virus 1 (strain 17)
gB (P10211)
gD (Q69091)
gH (P06477)
gL (P10185)