Del Valle Luis, White Martyn K, Khalili Kamel
Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, Philadelphia, Pennsylvania 19122, USA.
J Neuropathol Exp Neurol. 2008 Aug;67(8):729-40. doi: 10.1097/NEN.0b013e318180e631.
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.
人类多瘤病毒JC（JCV）是一种小型DNA肿瘤病毒，也是进行性多灶性白质脑病的病原体。在进行性多灶性白质脑病中，活跃的JCV复制会导致少突胶质细胞的溶解性破坏。正常的免疫系统可阻止JCV复制，并将病毒抑制在潜伏状态，因此无法检测到病毒蛋白的表达。在不允许病毒复制的细胞环境中，JCV可影响致癌转化。例如，将JCV接种到包括啮齿动物和猴子在内的实验动物中时具有高度致瘤性。在这些动物肿瘤中，有早期T抗原的表达，但没有晚期衣壳蛋白的表达，也没有病毒复制。此外，仅携带JCV T抗原的转基因小鼠会发生神经管起源的肿瘤。JCV基因组序列的检测以及病毒T抗原和Agno蛋白的表达表明，这种病毒可能与多种人类脑肿瘤和非中枢神经系统肿瘤有关。在此，我们讨论JCV致癌作用的相关机制，简要回顾支持和不支持该病毒在人类中枢神经系统肿瘤中起致病作用的研究，并确定未来研究的关键问题。
