Cytomegalovirus tegument protein pp65 (pp65)

Cytomegalovirus tegument protein pp65, also known as ppUL83, is the most abundant structural protein within the tegument of the Human Cytomegalovirus (HCMV) virion [4, 9]. It serves as a critical immunomodulatory factor that facilitates viral persistence by inhibiting the host's innate immune response, specifically by blocking the activation of interferon regulatory factor 3 (IRF-3) and modulating NF-κB signaling [12, 18]. Beyond its role in immune evasion, pp65 acts as a scaffold protein that optimizes the uploading of other proteins into viral particles during assembly and maturation [9]. Clinically, pp65 is the primary target of the host's cellular immune response, making it an essential component for diagnostic monitoring via the pp65 antigenemia test [14, 19]. It is also a major therapeutic target for the development of vaccines and adoptive T-cell therapies, particularly for preventing CMV disease in transplant recipients and as a tumor-specific antigen in glioblastoma [1, 5, 16]. Therapeutic strategies include DNA vaccines like ASP0113 and peptide vaccines like PEP-CMV, which aim to elicit robust CD4+ and CD8+ T-cell responses [4, 6, 8]. Additionally, small molecule modulators are being explored to inhibit pp65's function, thereby disrupting the viral life cycle and enhancing immune recognition [2, 7].

Other names

ppUL83UL8365 kDa lower matrix phosphoproteinHuman cytomegalovirus pp65HCMV pp65

Acts as an immunodominant antigen to stimulate host CD4+ and CD8+ T-cell responses; also targeted for inhibition to disrupt viral replication and immune evasion mechanisms.