Abstract
Cancer is the second leading cause of mortality worldwide. The study of DNA tumor-inducing viruses and their oncoproteins as a causative agent in cancer initiation and tumor progression has greatly enhanced our understanding of cancer cell biology. The initiation of oncogenesis is a complex process. Specific gene mutations cause functional changes in the cell that ultimately result in the inability to regulate cell differentiation and proliferation effectively. The human neurotropic Polyomavirus JC (JCV) belongs to the family Polyomaviridae and it is the causative agent of progressive multifocal leukoencephalopathy (PML), which is a fatal neurodegenerative disease in an immunosuppressed state. Sero-epidemiological studies have indicated JCV infection is prevalent in the population (85%) and that initial infection usually occurs during childhood. The JC virus has small circular, double-stranded DNA that includes coding sequences for viral early and late proteins. Persistence of the virus in the brain and other tissues, as well as its potential to transform cells, has made it a subject of study for its role in brain tumor development. Earlier observation of malignant astrocytes and oligodendrocytes in PML, as well as glioblastoma formation in non-human primates inoculated with JCV, led to the hypothesis that JCV plays a role in central nervous system (CNS) tumorigenesis. Some studies have reported the presence of both JC viral DNA and its proteins in several primary brain tumor specimens. The discovery of new Polyomaviruses such as the Merkel cell Polyomavirus, which is associated with Merkel cell carcinomas in humans, ignited our interest in the role of the JC virus in CNS tumors. The current evidence known about JCV and its effects, which are sufficient to produce tumors in animal models, suggest it can be a causative factor in central nervous system tumorigenesis. However, there is no clear association between JCV presence in CNS and its ability to initiate CNS cancer and tumor formation in humans. In this review, we will discuss the correlation between JCV and tumorigenesis of CNS in animal models, and we will give an overview of the current evidence for the JC virus’s role in brain tumor formation.
Highlights
The transformative properties of some viruses and their role in human cancers have been known for many decades
It is essential to underlay that the type of malignant transformations developed in murine models seems to be dependent on the strain of JC virus (JCV) [151,152,153,154]. These findings suggested the tumorigenic role of JCV large T antigen (LTAg)
Using high-through sequencing of tumor DNA obtained from urothelial carcinoma, the researchers identified the integration site of the BKV genome into exon 26 of myosin-binding protein C1 gene (MYBPC1) on chromosome 12 in tumor cells but not in normal renal cells
Summary
The transformative properties of some viruses and their role in human cancers have been known for many decades. The JC virus, BK virus, Simian virus 40 (SV40), and more recently discovered Merkel cell Polyomavirus (MCPyV) are some of the members in this group that infect humans and are known to either cause or have an association with human diseases and cancers These viruses are widespread, but most often only responsible for a clinically silent infection [6,7,8]. The understanding of the complex role these viruses play in brain tumor formation requires a wide variety of methods It remains a very active area of research due to the potential benefits of being able to treat better or prevent these cancers if a causative agent is identified. We present an overview of the current evidence for the JC virus’s role in brain tumor formation
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