JC virus: an oncogenic virus in animals and humans? | Semantic Scholar (2024)

The G144 oligodendrocyte cell line supports both infection by JC virus and robust levels of JCV DNA replication, and it is established that the Akt pathway regulates J CV DNA replication and that JCVDNA replication can be inhibited by MK2206, a compound that is specific for Akt.

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, but there is no clear association between JCV presence in CNS and its ability to initiate CNS cancer and tumor formation in humans.

JCV reactivation in nonpermissive cells after treatment with mAbs, such as intestinal epithelial cells in Crohn’s disease patients, in association with other host tumor-inducing factors, could provide valid information on the role of JCV in several malignancies,such as colorectal cancer.

This review focused on the potential association between JCV and BKV with brain and urinary tract tumors, respectively and found no direct involvement of PyVs in the development of human cancers.

Present evidence only supports the role of MCPyV as a carcinogen to humans, and a summarized discussion on the current knowledge concerning the roleof MCPYV, TSPyV, JCPy V and BKPyV in human cancers is presented.

Both spontaneous lens and lung tumor models provide good tools to investigate the oncogenic role of JCV T antigen and the alternative splicing of T antigen intron was detectable in αAT mice, gastric mucosa of KT mice, and various cells transfected with pEGFP-N1-T antigen.

Observations suggest that MCPyV can contribute to Merkel cell carcinoma pathogenesis and may therefore add a new virus to the list of human cancer viruses.

Immunosuppression drives increased brain JCV latency independent of systemic latency, as indicated by JCV viruria, in patients with non-PML progressive multifocal leukoencephalopathy.

The crystal structure of the origin-binding domain (OBD) of J CV T-antigen provides the first molecular understanding of JCV T-ag replication functions and suggests how the JCVT-ag OBD site-specifically binds to the major groove of GAGGC sequences in the origin.

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Direct evidence is provided that JCV is not strictly neurotropic but can infect CD34+ hematopoietic progenitor cells and those cells which have differentiated into a lymphocytic, but not monocytical, lineage.

Serological studies have shown that JCV is widespread throughout the human population, but infections are usually restricted by the immune system, particularly cell-mediated immunity, causing the virus to enter a latent phase, and an important corollary is that situations of severe immunosuppression may permit JCV to replicate and are thus a risk factor for PML.

The two human polyomavirus JC and BK are ubiquitous in the human population and whereas BKV is associated with severe urogenital disorders, JCV affects the CNS, leading to progressive multifocal leukoencephalopathy (PML).

Transgenic mice containing the early region of JCV(CY) induced tumor in transgenic mice to the human medulloblastoma/primitive neuroectodermal tumor (PNETs) in location, histologic appearance, and expression of marker proteins strongly suggests the utility of this novel animal model for the study of human brain tumors.

An anti-inflammatory compound, cyclosporine A, was found to inhibit JCV infection by preventing the activation of the transcription factor nuclear factor of activated T cells 4 (NFAT4), which suggests that calcium signaling and theactivation of NFAT in glial cells are required for J CV infection of the CNS.

It is demonstrated that JCV, unlike SV40, enters glial cells by receptor-mediated clathrin-dependent endocytosis, and is compared with that of the related polyomavirus, simian virus 40 (SV40).

The results from immunohistochemistry analysis revealed expression of JCV T-antigen in the nuclei of tumor cells in 28 (32.9%) of 85 tested samples, and gene amplification techniques using a pair of primers that recognize the JCV DNA sequence demonstrated the presence of the viral early sequence in 49 (69%) of 71 samples.

In a recent study of a pediatric PML patient, extensive rearrangement of the JCV TCR is detected in multiple tissues, and the archetype TCR was amplified from sites other than the kidney, indicating that this patient had suffered a dual infection.

The authors characterized the extent of JCV infection in Ficoll-gradient purified blood cells (peripheral blood mononuclear cells [PBMCs] of healthy and human immunodeficiency virus type 1 (HIV-1)-infected individuals and granulocytes were shown to be the predominant reservoir of J CV DNA harboring high copy numbers.

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