Potential mechanisms of the human polyomavirus JC in neural oncogenesis.
The human polyomavirus JC (JCV) is a small DNA tumor virus and the etiologic agent of the progressive multifocal leukoencephalopathy. In progressive multifocal leukoencephalopathy, active JCV replication causes the lytic destruction of oligodendrocytes. The normal immune system prevents JCV replication and suppresses the virus into a state of latency so that expression of viral proteins cannot be detected. In a cellular context that is nonpermissive for viral replication, JCV can affect oncogenic transformation. For example, JCV is highly tumorigenic when inoculated into experimental animals, including rodents and monkeys. In these animal tumors, there is expression of early T-antigen but not of late capsid proteins, nor is there viral replication. Moreover, mice transgenic for JCV T-antigen alone develop tumors of neural tube origin. Detection of JCV genomic sequences and expression of viral T-antigen and agnoprotein suggest a possible association of this virus with a variety of human brain and non-CNS tumors. Here, we discuss the mechanisms involved in JCV oncogenesis, briefly review studies that do and do not support a causative role for this virus in human CNS tumors, and identify key issues for future research.
Del Valle
Luis
L
Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, Philadelphia, Pennsylvania 19122, USA.
White
Martyn K
MK
Khalili
Kamel
K
D000818:Animals; D000957:Antigens, Viral, Tumor / Q000378:metabolism / Q000502:physiology; D016543:Central Nervous System Neoplasms / Q000209:etiology* / Q000821:virology*; D004195:Disease Models, Animal; D006801:Humans; D007577:JC Virus / Q000472:pathogenicity*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000209:etiology; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism / Q000502:physiology; D000086082:Viroporin Proteins
D000957:Antigens, Viral, Tumor; D054334:Viral Regulatory and Accessory Proteins; C042559:agnoprotein, polyomavirus; D000086082:Viroporin Proteins