Target intelligence / Profile preview

Human cytomegalovirus glycoprotein B (HCMV gB) (HCMV gB)

Target
HCMV gB
Molecular classification
Viral envelope protein, Class III viral fusion protein, Glycoprotein
01

Overview

Human cytomegalovirus glycoprotein B (HCMV gB), encoded by the UL55 gene, is an essential class III viral fusion protein required for the entry of the virus into host cells (UniProt P06473). It exists as a homotrimer on the viral envelope and mediates the fusion of the viral envelope with the host cell membrane through a series of complex conformational changes (Burke & Heldwein, 2015). Domain II of the gB ectodomain is a critical structural component that contains the Antigenic Domain 2 (AD-2), a site recognized by potent, broadly neutralizing antibodies (Pötzsch et al., 2011). Because of its indispensable role in both initial infection and subsequent cell-to-cell spread, gB is a primary target for the development of vaccines and therapeutic monoclonal antibodies. Therapeutic agents targeting Domain II specifically aim to block the fusion process, thereby preventing the delivery of the viral genome into the host cell. However, the presence of extensive glycosylation and the structural complexity of the protein present significant challenges for achieving high-level, durable immunity (Cui et al., 2018).

Other names
Envelope glycoprotein BUL55Antigenic Domain 2AD-2gB Domain II
02

Mechanism of action

Neutralization of viral infectivity by binding to the Antigenic Domain 2 (AD-2) of glycoprotein B to prevent the conformational transition from pre-fusion to post-fusion state, thereby inhibiting viral-cell membrane fusion.

03

Biological functions

Viral entryMembrane fusionCell-to-cell spreadHost cell attachment
04

Disease associations

Human cytomegalovirus infectionCongenital cytomegalovirus infectionOpportunistic infection in immunocompromised patients
05

Safety considerations

Strain-specific variation (genotypes 1-4)Potential for viral escape mutantsGlycan shielding of neutralizing epitopes
06

Interacting drugs

TRL345

3 more in the full profile.

07

Biomarkers

CMV DNA loadAnti-gB antibody titerAnti-AD-2 antibody levels

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