Human cytomegalovirus phosphoprotein 65 (pp65) (pp65)

Human cytomegalovirus phosphoprotein 65 (pp65), also known as pUL83, is the primary tegument protein of the Human Betaherpesvirus 5 (HCMV). It serves as a major immunodominant target for the host's cellular immune response, particularly CD8+ cytotoxic T lymphocytes (CTLs), making it a central focus for the development of HCMV vaccines and adoptive T-cell therapies. Beyond its role as a viral antigen, pp65 is involved in immune evasion by inhibiting the induction of interferon-beta and interfering with the cGAS-STING signaling pathway. In the context of oncology, pp65 is frequently detected in certain tumors, such as glioblastoma and medulloblastoma, where it is targeted by experimental immunotherapies like VBI-1901 and CMV-specific T-cells. The designation 'mimicked epitope only, no direct binding' refers to the protein's role in molecular mimicry, where specific pp65 peptides share structural homology with human self-antigens such as double-stranded DNA (dsDNA) and the Ro60 (SSA) autoantigen. This cross-reactivity is implicated in the pathogenesis of autoimmune diseases, particularly systemic lupus erythematosus (SLE), where anti-pp65 antibodies can cross-react with nuclear components. Furthermore, in some cancer immunotherapy contexts, the term may imply that the therapeutic agent targets a human mimic rather than the native viral protein, raising significant safety concerns regarding off-target autoimmunity.

Other names

UL8365 kDa matrix phosphoproteinLower matrix phosphoproteinHCMV pp65pUL83Phosphoprotein 65