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

Human cytomegalovirus (HCMV) 65 kDa lower matrix phosphoprotein, encoded by the UL83 gene and commonly known as pp65, is the most abundant tegument protein of the HCMV virion and a primary target of the host immune response (UniProt P06725). It plays a dual role in viral pathogenesis: it facilitates viral entry and assembly while simultaneously acting as a potent immunomodulator that can inhibit the host's interferon response and interfere with MHC class I and II antigen presentation pathways to evade immune detection (PubMed: 16227268). Despite these evasion tactics, pp65-derived peptides are the dominant epitopes recognized by CD8+ cytotoxic T lymphocytes and CD4+ helper T cells in HCMV-seropositive individuals (PubMed: 8523568). Consequently, pp65 is a critical target for the development of diagnostic assays (such as the pp65 antigenemia test), prophylactic vaccines (e.g., mRNA-1647), and adoptive T-cell therapies (e.g., Posoleucel) designed to restore CMV-specific immunity in immunocompromised patients, such as hematopoietic stem cell or solid organ transplant recipients (ClinicalTrials.gov: NCT04356612). Therapeutic interventions typically focus on using these epitopes to expand T-cell populations ex vivo or to prime the immune system to recognize and eliminate CMV-infected cells.

Other names

UL8365 kDa matrix phosphoproteinTegument protein pp65Phosphoprotein 65HCMV UL83

Stimulation of T-cell receptor (TCR) recognition of pp65-derived epitopes presented on MHC molecules to induce a targeted cytotoxic and helper T-cell immune response against HCMV-infected cells.