Cytomegalovirus matrix phosphoprotein pp65 (pp65)

Cytomegalovirus matrix phosphoprotein pp65, encoded by the UL83 gene, is the most abundant tegument protein of Human Cytomegalovirus (HCMV) and a critical factor in viral pathogenesis. It functions as a major immune evasion protein by inhibiting the host's innate antiviral response, specifically by blocking the nuclear translocation of interferon regulatory factor 3 (IRF3) and inactivating the DNA sensor cGAS (UniProt P06725). Additionally, pp65 acts as a scaffold protein for viral assembly and facilitates the transactivation of viral immediate-early genes (PubMed 1.5.1, 1.5.4). Despite its role in evasion, pp65 is the primary immunodominant target for the host's cellular immune response, making it a central focus for diagnostic and therapeutic applications (PubMed 1.1.1). The pp65 antigenemia assay is a standard clinical biomarker used to detect active CMV replication in immunocompromised patients by identifying the protein within peripheral blood leukocytes (PubMed 1.2.4). In the therapeutic landscape, pp65 is targeted by various vaccines and adoptive T-cell therapies designed to restore or enhance CMV-specific immunity in transplant recipients and to treat pp65-expressing malignancies like glioblastoma (PubMed 1.4.1, 1.3.4). While these interventions are generally well-tolerated, clinical trials in brain tumors have noted potential safety concerns, including cerebral edema and encephalopathy (PubMed 1.3.3).

Other names

65 kDa phosphoproteinPhosphoprotein UL83Tegument protein UL83Lower matrix phosphoproteinppUL8365 kDa matrix phosphoprotein

Induction of antigen-specific cellular immunity, primarily through the activation of CD8+ cytotoxic T lymphocytes and CD4+ helper T cells, which recognize pp65-derived peptides presented on MHC molecules to eliminate CMV-infected or pp65-expressing cells.