Human cytomegalovirus 65 kDa phosphoprotein (pp65) (HCMV pp65)

Human cytomegalovirus (HCMV) 65 kDa phosphoprotein, or pp65 (encoded by the UL83 gene), is the most abundant tegument protein of the virus and a primary target of the cellular immune response (UniProt P06725). It plays a significant role in modulating the host's initial innate immune response by inhibiting the induction of interferon-responsive genes and interfering with the presentation of other viral antigens (PubMed: 15596814). During infection, pp65 is processed by the proteasome, and its derived peptides, most notably the NLVPMVATV epitope, are presented on the cell surface by HLA-A*02:01 molecules (PubMed: 10811002). This peptide-HLA complex is the principal target for CD8+ cytotoxic T-lymphocytes, which are essential for controlling HCMV latency and reactivation. Consequently, pp65 is a focal point for therapeutic development, including adoptive T-cell therapies and vaccines like Triplex, which aim to bolster CMV-specific immunity in transplant recipients (ClinicalTrials.gov: NCT02506933). These interventions leverage the high immunogenicity of pp65 to provide protection against CMV-related complications in immunocompromised patients. The target is also explored in oncology, as pp65 is expressed in certain tumors like glioblastoma, making it a candidate for cancer vaccines such as VBI-1901 (PubMed: 30232150). Monitoring pp65-specific T-cell levels and antigenemia remains a standard practice for managing CMV-related risks.

Other names

UL8365 kDa phosphoproteinTegument protein pp65Phosphoprotein 65Lower matrix protein

Induction of antigen-specific T-cell responses and direct T-cell mediated lysis of infected cells presenting pp65 peptides on HLA molecules.