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Human cytomegalovirus pp65 (UL83) is the most abundant tegument protein and a major constituent of extracellular virions; while not essential for replication in fibroblasts, it contributes to tegument assembly as an optional scaffold and influences incorporation of other viral proteins. It is a dominant target of humoral and cellular immunity, especially CD8+ cytotoxic T lymphocytes. pp65 modulates host innate antiviral defenses by inhibiting IRF3 activation and dampening IFN-responsive gene induction, and it can reduce NF-κB activation/nuclear translocation, thereby facilitating immune evasion. Because pp65-specific CTLs recognize pp65-derived peptides presented by MHC class I and kill infected cells through granule exocytosis (perforin/granzymes) and Fas–FasL pathways, pp65 is widely used as an antigen in HCMV vaccines and adoptive T-cell therapies rather than as a classical drug target.
Vaccine/adoptive T-cell therapy context: pp65 serves as an immunodominant antigen to elicit or transfer pp65-specific CD8+ T cells that kill HCMV-infected cells via perforin/granzyme and Fas–FasL pathways.
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