Oncogenic potential of human neurotropic papovavirus, JCV, in CNS.
The human polyomavirus, JCV, is the causative agent of Progressive Multifocal Leukoencephalopathy (PML), a fatal human demyelinating disease. PML results from the cytolytic destruction of oligodendrocytes, the myelin-producing cells of the nervous system. JCV has also been shown to be tumorigenic in several animal models. Transgenic mice expressing the JCV early protein, T-antigen, develop poorly differentiated neural crest origin tumours. Intracerebral inoculation of JCV into newborn hamsters induces medulloblastomas, astrocytomas, and primitive neuroectodermal tumours. Further, inoculation of the virus into the brains of non-human primates, owl and squirrel monkeys, results in astrocytomas and glioblastoma multiforme. Several case reports have associated JCV with human CNS tumours in patients with concomitant PML, and one such report has detected JCV in a glial tumour in the absence of PML. The induction of neural origin tumours by JCV has been studied in transgenic mice harbouring the early genome of the virus. Alterations in the level and function of tumour suppressor proteins p53 and Rb, as well as associated cell cycle regulators, have been detected in tumour tissue from JCV T-antigen transgenic mice. Possible mechanisms by which JCV may exert its oncogenic potential by alteration of cellular growth control pathways in both humans and experimental animals are discussed.
Gordon
J
J
Center for NeuroVirology and NeuroOncology, Allegheny University of the Health Sciences, Philadelphia, PA 19102, USA.
Krynska
B
B
Otte
J
J
Houff
S A
SA
Khalili
K
K
D000818:Animals; D016543:Central Nervous System Neoplasms / Q000821:virology*; D006801:Humans; D007577:JC Virus / Q000472:pathogenicity*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000821:virology; D014412:Tumor Virus Infections / Q000473:pathology*