Expression of JC virus regulatory proteins in human cancer: Potential mechanisms for tumourigenesis

JC virus (JCV) is a human polyomavirus that is the etiologic agent of the fatal demyelinating disease of the central nervous system known as progressive multifocal leukoencephalopathy (PML). JCV is also linked to some tumours of the brain and other organs as evidenced by the presence of JCV DNA sequences and the expression of viral proteins in clinical samples. Since JCV is highly oncogenic in experimental animals and transforms cells in culture, it is possible that JCV contributes to the malignant phenotype of human tumours with which it is associated. JCV encodes three non-capsid regulatory proteins: large T-antigen, small t-antigen and agnoprotein that interact with a number of cellular target proteins and interfere with certain normal cellular functions. In this review, we discuss how JCV proteins deregulate signalling pathways especially ones pertaining to transcriptional regulation and cell cycle control. These effects may be involved in the progression of JCV-associated tumours and may represent potential therapeutic targets. (c) 2005 Elsevier Ltd. All rights reserved.