Cancer Inducing Role of BK Polyomavirus Large T Antigen: Molecular Signaling View

The BK polyomavirus (BKPyV), a ubiquitous human pathogen, has garnered significant attention for its potential oncogenic role, particularly in immunocompromised populations such as transplant recipients. This review synthesizes current evidence on the molecular mechanisms underlying BKPyV-associated carcinogenesis, with a focus on the viral Large T antigen (LT-Ag). LT-Ag drives oncogenic transformation primarily by inactivating tumor suppressor proteins p53 and pRb, disrupting cell cycle regulation, and inhibiting apoptosis. Additionally, it dysregulates critical signaling pathways, including Wnt/β-catenin, PI3K/Akt/mTOR, Ras/Raf/MAPK, and STAT-3, which collectively promote uncontrolled proliferation, survival, and genomic instability. A hallmark of BKPyV's oncogenicity is its capacity to integrate into the host genome, often near tumor suppressor loci, further amplifying chromosomal damage. Clinically, BKPyV has been implicated in urothelial carcinoma, renal cell carcinoma, and prostate cancer, with viral DNA and LT-Ag detected in 20-50% of tumor specimens from kidney transplant recipients (KTRs). However, epidemiological data remain contentious, as studies in immunocompetent cohorts report inconsistent associations, and viral presence in non-neoplastic tissues complicates causal interpretations. This duality BKPyV as both a latent commensal and a potential oncogenic driver underscores the need for nuanced investigation into host-virus interactions, particularly in the context of immunosuppression. Emerging diagnostic approaches, such as next-generation sequencing to map viral integration sites, and therapeutic strategies targeting LT-Ag-mediated pathways hold promise for early detection and intervention. By bridging molecular insights with clinical observations, this review advocates for longitudinal studies to clarify BKPyV's role in carcinogenesis and to refine management protocols for high-risk populations, ultimately mitigating the burden of virus-associated malignancies.