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The Cytomegalovirus 65 kDa phosphoprotein (pp65), encoded by the UL83 gene, is the most abundant tegument protein of the Human Cytomegalovirus (HCMV) (UniProt P06725). It plays a critical role in viral pathogenesis by modulating the host's innate immune response, specifically by inhibiting the induction of interferon-stimulated genes through interaction with the DNA sensor IFI16 (PubMed: 25132684). While not a traditional enzyme or receptor target for small molecule inhibition, pp65 is a highly significant target in the field of vaccinology and adoptive immunotherapy because it is the dominant protein recognized by the host's cytotoxic T-lymphocytes (CTLs) during natural infection (PubMed: 11506829). \n\nClinically, pp65 is used both as a diagnostic biomarker through the 'pp65 antigenemia assay' to monitor CMV load in immunocompromised patients and as a therapeutic target in the development of CMV vaccines and T-cell therapies (PubMed: 30206138). Research also suggests a potential association between pp65 expression and certain malignancies, such as glioblastoma, making it a target for experimental cancer immunotherapies. Its role in immune evasion and its high immunogenicity make it a cornerstone for strategies aiming to prevent or treat CMV-associated diseases in transplant recipients and neonates.
pp65 serves as a primary antigenic target for the induction of CD8+ and CD4+ T-cell mediated immunity. Vaccines and immunotherapies utilizing pp65 aim to stimulate the host immune system to recognize and eliminate CMV-infected cells or cells expressing viral antigens.
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