Herpes simplex virus type 1 glycoprotein D (gD)

Herpes simplex virus type 1 (HSV-1) glycoprotein D (gD) is a critical envelope protein essential for the virus's ability to enter host cells and spread between them [2, 4]. It serves as the primary receptor-binding protein, interacting with host cell surface molecules such as Nectin-1, Herpesvirus Entry Mediator (HVEM), and 3-O-sulfated heparan sulfate [2, 3]. This binding triggers a cascade of conformational changes that activate the viral fusion machinery, including glycoproteins B (gB) and H/L (gH/gL), facilitating the fusion of the viral envelope with the host cell membrane [7, 18]. Due to its prominent role in the initial stages of infection and its status as a major immunodominant antigen, gD is a central target for the development of vaccines and neutralizing monoclonal antibodies [1, 15]. Clinical candidates like UB-621 and various recombinant subunit vaccines target gD to prevent primary infection and reduce the frequency of viral reactivation [1, 15]. While numerous candidates have entered clinical trials, achieving long-term sterilizing immunity remains a significant challenge due to the virus's ability to establish lifelong latency in sensory neurons [13, 17].

Other names

Glycoprotein DgDgD-1US6 proteinEnvelope glycoprotein DHHV-1 gDHSV-1 gD

Neutralization of viral entry and cell-to-cell spread by blocking the interaction between glycoprotein D and host receptors such as Nectin-1 and HVEM, thereby preventing the trigger for membrane fusion [1, 8].