Passerini Sara, Messina Sara, De Angelis Marta, Nencioni Lucia, Gianno Francesca, Antonelli Manila, Pietropaolo Valeria
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, 00185, Italy.
Department of Public Health and Infectious Diseases, Sapienza University, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Rome, Italy.
J Neurovirol. 2025 Sep 17. doi: 10.1007/s13365-025-01274-7.
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.
JC多瘤病毒（JCPyV）与进行性多灶性白质脑病（PML）相关，但其在脑癌中可能发挥的作用也存在争议。一种介导细胞转化的候选蛋白是大T抗原（LTAg），它能够结合Wnt信号通路蛋白β-连环蛋白，从而使细胞周期失调。在本研究中，我们调查了小儿脑肿瘤中JCPyV的存在情况和分子状态，以及病毒阳性对Wnt信号通路的影响。在101例脑肿瘤中有31例（30.7%）检测到JCPyV DNA，病毒载量为3.2拷贝/细胞。扩增的非编码控制区（NCCR）显示为原型序列，VP1与参考菌株具有高度同源性。所有JCPyV阳性肿瘤均检测到LTAg基因。有趣的是，其中5个组织未表达VP1和病毒微小RNA（miRNA），提示晚期区域转录受到阻碍。与阴性组织相比，JCPyV阳性组织中β-连环蛋白、c-myc和细胞周期蛋白D1表达上调，表明该病毒可能利用此信号通路，潜在地促进脑癌发生。本研究进一步证明了JCPyV在人类脑肿瘤中的流行情况，并报道了Wnt信号通路的改变，为进一步研究JCPyV介导的脑肿瘤发生奠定了基础。
