Delbue Serena, Comar Manola, Ferrante Pasquale
Department of Biomedical, Surgical and Dental Sciences, University of Milano, Via Pascal, 36-20133 Milan, Italy.
Department of Medical Sciences, University of Trieste, Trieste, Italy.
Infect Agent Cancer. 2017 Feb 3;12:10. doi: 10.1186/s13027-017-0122-0. eCollection 2017.
Almost one fifth of human cancers worldwide are associated with infectious agents, either bacteria or viruses, and this makes the possible association between infections and tumors a relevant research issue. We focused our attention on the human Polyomavirus JC (JCPyV), that is a small, naked DNA virus, belonging to the family. It is the recognized etiological agent of the Progressive Multifocal Leukoencephalopathy (PML), a fatal demyelinating disease, occurring in immunosuppressed individuals. JCPyV is able to induce cell transformation in vitro when infecting non-permissive cells, that do not support viral replication and JCPyV inoculation into small animal models and non human primates drives to tumor formation. The molecular mechanisms involved in JCPyV oncogenesis have been extensively studied: the main oncogenic viral protein is the large tumor antigen (T-Ag), that is able to bind, among other cellular factors, both Retinoblastoma protein (pRb) and p53 and to dysregulate the cell cycle, but also the early proteins small tumor antigen (t-Ag) and Agnoprotein appear to cooperate in the process of cell transformation. Consequently, it is not surprising that JCPyV genomic sequences and protein expression have been detected in Central Nervous System (CNS) tumors and colon cancer and an association between this virus and several brain and non CNS-tumors has been proposed. However, the significances of these findings are under debate because there is still insufficient evidence of a casual association between JCPyV and solid cancer development. In this paper we summarized and critically analyzed the published literature, in order to describe the current knowledge on the possible role of JCPyV in the development of human tumors.
全球近五分之一的人类癌症与感染因子有关，这些感染因子可以是细菌或病毒，这使得感染与肿瘤之间的潜在关联成为一个相关的研究问题。我们将注意力集中在人多瘤病毒JC（JCPyV）上，它是一种小型无包膜DNA病毒，属于该病毒家族。它是进行性多灶性白质脑病（PML）公认的病原体，PML是一种发生在免疫抑制个体中的致命性脱髓鞘疾病。当JCPyV感染不支持病毒复制的非允许细胞时，它能够在体外诱导细胞转化，并且将JCPyV接种到小动物模型和非人类灵长类动物中会导致肿瘤形成。JCPyV致癌作用所涉及的分子机制已得到广泛研究：主要的致癌病毒蛋白是大T抗原（T-Ag），它能够与视网膜母细胞瘤蛋白（pRb）和p53等多种细胞因子结合，并失调细胞周期，但早期蛋白小T抗原（t-Ag）和Agno蛋白似乎也在细胞转化过程中发挥协同作用。因此，在中枢神经系统（CNS）肿瘤和结肠癌中检测到JCPyV基因组序列和蛋白表达，并且有人提出该病毒与几种脑肿瘤和非CNS肿瘤之间存在关联，这并不奇怪。然而，这些发现的意义仍在争论中，因为仍然没有足够的证据证明JCPyV与实体癌发展之间存在因果关系。在本文中，我们总结并批判性地分析了已发表的文献，以描述目前关于JCPyV在人类肿瘤发生中可能作用的知识。
