Target intelligence / Profile preview

65 kDa phosphoprotein (pp65) (pp65)

Target
pp65
Molecular classification
Viral structural protein, Tegument protein, Phosphoprotein, Viral immune modulator
01

Overview

The 65 kDa phosphoprotein (pp65), encoded by the UL83 gene, is the most abundant tegument protein of Human Cytomegalovirus (HCMV) and a key factor in viral pathogenesis [1, 3]. It primarily functions as an immune modulator by inhibiting host innate immune pathways, specifically preventing the activation and nuclear translocation of Interferon Response Factor 3 (IRF3) and inactivating the DNA sensor cGAS [2, 22]. While dispensable for viral replication in fibroblasts, pp65 is essential for efficient growth in macrophages and plays a structural role in virion morphogenesis as a scaffold protein [1, 25]. Clinically, pp65 is an immunodominant antigen, serving as the basis for the "pp65 antigenemia assay" used to monitor viral load and guide preemptive therapy in transplant recipients [7, 14]. Due to its high immunogenicity, it is a primary target for the development of CMV vaccines and adoptive T-cell therapies [5, 12, 17]. Furthermore, its expression in various malignancies, such as glioblastoma, has positioned it as a prominent target for experimental cancer immunotherapies [16, 27].

Other names
UL83Phosphoprotein 65Tegument protein UL8365 kDa matrix phosphoproteinppUL83Phosphoprotein UL83
02

Mechanism of action

Induction of antigen-specific T-cell mediated immunity and direct recognition/lysis of HCMV-infected cells by adoptive or vaccine-induced T-cells.

03

Biological functions

Inhibition of host interferon responseSuppression of IRF3 and cGAS signalingTransactivation of viral immediate-early genesVirion morphogenesis and tegument assemblyImmune evasionInhibition of IFI16-mediated DNA sensing
04

Disease associations

Human Cytomegalovirus (HCMV) infectionOpportunistic infection in immunocompromised hostsCongenital cytomegalovirus infectionGlioblastoma multiforme
05

Safety considerations

Cytokine Release Syndrome (CRS)Graft-versus-Host Disease (GvHD) in allogeneic settingsPotential for viral immune escape through protein mutationCerebral edema or neuroinflammation (in brain tumor contexts)
06

Interacting drugs

Posoleucel (ALVR109)

5 more in the full profile.

07

Biomarkers

pp65 antigenemiapp65-specific IFN-gamma ELISpotCMV pp65-specific T-cell frequency

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