Herpes simplex virus 2 fusion machinery (HSV-2 gB/gH/gL)

The Herpes simplex virus 2 (HSV-2) fusion machinery is a multi-component protein system required for the virus to penetrate host cell membranes and establish infection. This machinery is composed of the core fusion proteins: glycoprotein B (gB), which serves as the Class III viral fusogen, and the glycoprotein H/glycoprotein L (gH/gL) heterodimer, which acts as a regulator of gB activity [1, 5]. In most cell types, the fusion process is initiated by glycoprotein D (gD), which binds to host cell receptors such as Nectin-1 or Herpesvirus Entry Mediator (HVEM), triggering a cascade of conformational changes in gH/gL and subsequently gB [1, 6]. This cascade culminates in the insertion of gB fusion loops into the host membrane and the merging of the viral envelope with the host plasma membrane or endosomal membrane. As an essential and highly conserved apparatus for both initial infection and cell-to-cell spread, the HSV-2 fusion machinery is a primary target for therapeutic intervention. Current strategies include the use of monoclonal antibodies (e.g., UB-621) that block receptor binding or fusion triggering, and vaccines (e.g., GSK3858279, mRNA-1608) designed to elicit neutralizing antibodies against gD, gB, or the gH/gL complex [2, 7]. While drugs like docosanol provide a topical means of inhibiting fusion, systemic efforts focus on reducing viral shedding and preventing the recurrence of genital herpes by neutralizing the virus before it can enter new cells [8, 9]. Citations: [1] Eisenberg et al. (2012) PubMed; [2] ClinicalTrials.gov NCT04714060; [3] UniProt P08357; [4] Johnston et al. (2014) PubMed; [5] Chowdary et al. (2010) Nature; [6] Connolly et al. (2011) J Virol; [7] Moderna Pipeline (2024); [8] Pope et al. (1998) PubMed; [9] GSK Pipeline (2024).

Other names

HSV-2 entry complexHSV-2 gB/gH/gL complexHerpes simplex virus 2 glycoprotein complexHSV-2 core fusion machinery

Inhibition of viral-cell membrane fusion by blocking the conformational changes of glycoprotein B or preventing the interaction between glycoprotein D and host receptors [1, 2].