Review on the role of the human Polyomavirus JC in the development of tumors.
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 thePolyomaviridaefamily. 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.
Department of Biomedical, Surgical and Dental Sciences, University of Milano, Via Pascal, 36-20133 Milan, Italy.
Serena
0000-0002-3199-9369
S
Delbue
Department of Medical Sciences, University of Trieste, Trieste, Italy.|Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", 34137 Trieste, Italy.
Manola
M
Comar
Department of Biomedical, Surgical and Dental Sciences, University of Milano, Via Pascal, 36-20133 Milan, Italy.|Istituto Clinico Città Studi, Milan, Italy.
Pasquale
P
Ferrante
Central nervous system tumors; Colon cancer; JC virus