Herpes simplex virus glycoprotein D2 (gD2)

Herpes simplex virus glycoprotein D2 (gD2) is a critical envelope protein of the Herpes Simplex Virus type 2 (HSV-2), the primary cause of genital herpes (NIH: PMC4354957). It plays an essential role in the viral life cycle by mediating the attachment and entry of the virus into host cells through interactions with specific cellular receptors, including herpesvirus entry mediator (HVEM) and nectin-1 (PubMed: 9223502, NIH: PMC191868). This binding triggers a conformational change in gD2 that subsequently activates the gH/gL and gB fusion machinery, allowing the viral envelope to fuse with the host cell membrane (MDPI: Viruses 2025, 17(2), 249). Due to its high immunogenicity and central role in infection, gD2 has been the primary target for numerous prophylactic and therapeutic vaccine candidates, such as the gD2-AS04 (Herpevac) subunit vaccine (NIH: PMC1317600). While these vaccines have successfully induced high titers of neutralizing antibodies in clinical trials, they have largely failed to provide robust protection against HSV-2 acquisition in humans, highlighting significant challenges in overcoming viral immune evasion and preventing the establishment of latency (eLife 2015;4:e06054). Current therapeutic strategies continue to target gD2 using monoclonal antibodies like HDIT101 and UB-621, as well as multi-antigen vaccine formulations, to improve clinical outcomes (Frontiers in Immunology 2025).

Other names

gD-2Envelope glycoprotein DUS6Glycoprotein D-2

Neutralization of viral particles and inhibition of viral entry into host cells by blocking the interaction between gD2 and its cellular receptors, such as HVEM and Nectin-1 (NIH: PMC5643598).