The presence of human polyomavirus JC (JCPyV) in pediatric brain tumors: a plausible trigger in Wnt/β-catenin pathway.

Abstract

JC polyomavirus (JCPyV) is associated with progressive multifocal leukoencephalopathy (PML), but its plausible role in brain cancers is also disputed. One candidate to mediate cell transformation is the Large T antigen (LTAg), which has the capability to bind the Wnt pathway protein β-catenin, thus deregulating the cell cycle. In the current study, we investigated the presence and molecular state of JCPyV in pediatric brain tumors and the effects of virus-positivity on the Wnt pathway. JCPyV DNA was found in 31/101 (30.7%) brain tumors with a viral load of 3.2 copies/cell. The amplified NCCR revealed an archetype sequence, and VP1 reported a high degree of homology with the reference strain. The LTAg gene was reported in all JCPyV-positive tumors. Interestingly, among them, 5 tissues did not express VP1 and viral miRNAs, supporting a hampering of late region transcription. Over-expression of β-catenin, c-myc and cyclin D1 was observed in JCPyV-positive tissues compared to negative ones, suggesting that the virus may exploit this signaling pathway, potentially contributing to brain carcinogenesis. The current study adds further evidence of JCPyV prevalence in human brain tumors and reports alterations of the Wnt pathway, laying the basis for further investigation on JCPyV-mediated oncogenesis in the brain.