JC Virus: An oncogenic virus in animals and humans?

Abstract

JCV is a human polyomavirus of the Polyomaviridae family, which also includes BK virus and simian vacuolating virus 40 (SV40). JC virus (JCV) was first isolated in 1971 from the brain of a patient with Progressive Multifocal Leukoencephalopathy (PML). Like other polyomaviruses, JCV has a restricted host range. The virus infects the majority of the human population with seroconversion occurring during adolescence. JCV has a limited and specific tissue tropism infecting the kidney and oligodendrocytes and astrocytes in the central nervous system (CNS). Initial JCV infection is generally asymptomatic in immunocompetent hosts, and it establishes a persistent infection in the kidney and possibly bone marrow. In immunocompromised individuals JCV can cause a lytic infection in the CNS and lead to development of the fatal, demyelinating disease PML. The name polyoma is derived from the Greek terms: poly, meaning many, and oma, meaning tumors, owing to the capacity of this group of viruses to cause tumors. JCV inoculation of small animal models and non-human primates, which are not permissive to a productive JCV infection, leads to tumor formation. Given the ubiquitous nature of the virus and its strong association with cancer in animal models, it is hypothesized that JCV plays a role in human cancers. However, the role for JCV in human cancers and tumor formation is not clear. Some researchers have reported an association of JCV with human cancers including brain tumors, colorectal cancers, and cancers of the gastrointestinal tract, while other groups report no correlation. Here, we review the role of JCV in cancers in animal models and present the findings on JCV in human cancers.

Epidemiology of Simian Polyomavirus SV40 in Different Areas of Russian Federation (RF)

“…Later 3 more polyomaviruses were isolated: KI, Wu from respiratory tract and MCV from rare malignant skin tumor -Merkel carcinoma (Feng et al, 2008) Among human viruses such ubiquitous viruses as JCV and BKV are widely known and are determined from 60 to 90% of cases in humans according to data of different authors (Knowles et al, 2006;Maginnis & Atwood, 2009). …”

The use of mathematical and computational models to define the role of mutation and infection in colorectal cancer.

“…After attachment, JCV enters the cell via clathrin-dependent endocytosis, a process in which the virus is internalized through the inward budding of the plasma membrane, forming clathrin coated pits [47,82]. JCV is then delivered to endosomes and caveosomes, facilitating the movement of the virus to the endoplasmic reticulum, where viral un-coating is occurs [82].…”

“…JCV is then delivered to endosomes and caveosomes, facilitating the movement of the virus to the endoplasmic reticulum, where viral un-coating is occurs [82]. Finally, JCV is translocated to the nucleus [82].…”

“…Once inside the nucleus, the transcription factors API, NF-1, NF-KB, NFAT, and YB-1 bind to JCV's promoter region, leading to the transcription of early region mRNAs, and eventually translation in the cytoplasm [82]. After translation, T-ag accumulates to high concentrations and initiates cellular division by inhibiting pRb (see below for more details).…”

“…Given these results, the authors proposed the following "hit and run" scenario for ICV- Despite the evidence presented Chapter 3, the Infection model is contentious because it is difficult to determine role of JCV in colorectal caner. A primary reason for this is that JCV is so prevalent that it is not entirely surprising that JCV can be found in tumors [82]. It could simply be that JCV latently infects healthy cells and but remains detectable in the tissue after tumor formation.…”