Target intelligence / Profile preview

Herpes simplex virus type 2 glycoprotein H (gH)

Target
gH
Molecular classification
Viral glycoprotein, Type I membrane protein, Fusion machinery component
01

Overview

Herpes simplex virus type 2 (HSV-2) glycoprotein H (gH) is an essential envelope protein that forms a stable heterodimer with glycoprotein L (gL) [1, 4]. This gH/gL complex is a central component of the core fusion machinery, which also includes glycoprotein B (gB) and glycoprotein D (gD) [7, 18]. gH/gL acts as a critical adaptor that transmits the triggering signal from gD, upon receptor binding, to gB, which then executes the fusion of the viral envelope with the host cell membrane [9, 38]. Beyond its role in fusion, gH/gL also interacts with host cell integrins, such as αVβ3, to facilitate entry into specific cell types [1, 4]. Because it is indispensable for viral infectivity and spread, gH is a major target for the development of neutralizing monoclonal antibodies and subunit or replication-defective vaccines [2, 31, 33]. Therapeutic strategies targeting gH aim to block the activation of the fusion machinery, thereby preventing the establishment and spread of HSV-2 infection [25, 28].

Other names
Envelope glycoprotein HgHgH2UL22gH/gL complex
02

Mechanism of action

Neutralization of viral entry by blocking the gH/gL complex's ability to activate the gB fusogen or by preventing its interaction with host cell receptors and integrins [2, 25, 33].

03

Biological functions

Viral entryMembrane fusiongB activationHost cell attachmentInteraction with host integrins
04

Disease associations

InfectionGenital herpesNeonatal herpesEncephalitis
05

Safety considerations

Immune evasionCross-reactivity with other herpesvirusesHeterodimer stability requirements for effective immunization
06

Interacting drugs

gH-deleted replication-defective vaccine (experimental)

2 more in the full profile.

07

Biomarkers

Anti-gH antibodiesHSV-2 DNAgH-specific T-cell response

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