scholarly journals Primary Central Nervous System Lymphoma Expressing the Human Neurotropic Polyomavirus, JC Virus, Genome

2004 ◽  
Vol 78 (7) ◽  
pp. 3462-3469 ◽  
Author(s):  
Luis Del Valle ◽  
Sahnila Enam ◽  
Cesar Lara ◽  
Judith Miklossy ◽  
Kamel Khalili ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
B Lymphocytes ◽  
Dna Sequences ◽  
Jc Virus ◽  
T Antigen ◽  
Viral Capsid ◽  
Polyomavirus Jc ◽  
Positive Immunoreactivity ◽  
Viral Capsid Proteins

ABSTRACT B lymphocytes are known as a potential site for latency and reactivation of the human neurotropic polyomavirus, JC virus (JCV). In light of recent studies on the oncogenicity of JCV and the transforming ability of the JCV early protein, T antigen, we investigated the association of JCV with B-cell lymphomas of the central nervous system. Examination of 27 well-characterized clinical specimens by gene amplification and immunohistochemistry revealed the presence of DNA sequences corresponding to the JCV early genome and the late Agnoprotein in 22 samples and the JCV late genome encoding the viral capsid proteins in 8 samples. Expression of T antigen and that of Agnoprotein by immunohistochemistry were each detected in six specimens. No evidence of the production of viral capsid proteins was observed, ruling out productive infection of JCV in the tumor cells. The results from laser capture microdissection verified the presence of JCV T-antigen sequences in tumor cells with positive immunoreactivity to antibodies against the viral proteins T antigen and Agnoprotein. Due to previous reports demonstrating an association of the Epstein-Barr virus (EBV) with transformation of B lymphocytes, EBV DNA sequences and the EBV transforming protein, latent membrane protein 1 (LMP1), were analyzed in parallel. EBV LMP1 DNA sequences were detected in 16 of 23 samples, and LMP1 expression was detected in 16 samples, 5 of which exhibited positive immunoreactivity to JCV proteins. Double labeling demonstrated coexpression of JCV T antigen and EBV LMP1 in the same cells. The detection of the JCV genome in large numbers of B-cell lymphomas and its coexistence with EBV suggest a potential role for JCV in the pathogenesis of primary CNS lymphoma.

scholarly journals The Role of the JC Virus in Central Nervous System Tumorigenesis

2020 ◽  
Vol 21 (17) ◽  
pp. 6236
Author(s):  
Nicholas Ahye ◽  
Anna Bellizzi ◽  
Dana May ◽  
Hassen S. Wollebo
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Tumor ◽  
Animal Models ◽  
Causative Agent ◽  
Jc Virus ◽  
Tumor Formation ◽  
Current Evidence ◽  
Merkel Cell

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.

Immunology of Multiple Sclerosis

2016 ◽  
Author(s):  
Laura Piccio ◽  
Anne H. Cross
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Monoclonal Antibodies ◽  
B Lymphocytes ◽  
Autoimmune Disorder ◽  
Innate Immune ◽  
Immune Systems ◽  
The Central Nervous System ◽  
Multiple Sclerosis Treatment

Multiple sclerosis (MS) is considered to be an autoimmune disease of the central nervous system that targets myelin but affects both white matter and gray matter. Multiple sclerosis is thought to be mediated by cells of the adaptive and innate immune systems. CD4+ T lymphocytes of the Th1 and Th17 subtypes are believed to be critical for the initiation of multiple sclerosis. Treatment with monoclonal antibodies that deplete B lymphocytes has proven that B cells are critical to relapse development in multiple sclerosis. While immunopathophysiology is clearly important in MS, whether multiple sclerosis is truly an autoimmune disorder and the target or targets of the autoimmunity remain unknown.

Activated leukocyte cell adhesion molecule regulates B lymphocyte migration across central nervous system barriers

2019 ◽  
Vol 11 (518) ◽  
pp. eaaw0475 ◽  
Author(s):  
Laure Michel ◽  
Camille Grasmuck ◽  
Marc Charabati ◽  
Marc-André Lécuyer ◽  
Stephanie Zandee ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cell Adhesion ◽  
B Lymphocytes ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
B Lymphocyte ◽  
Peripheral Circulation ◽  
Lymphocyte Migration ◽  
Anti Cd20

The presence of B lymphocyte–associated oligoclonal immunoglobulins in the cerebrospinal fluid is a classic hallmark of multiple sclerosis (MS). The clinical efficacy of anti-CD20 therapies supports a major role for B lymphocytes in MS development. Although activated oligoclonal populations of pathogenic B lymphocytes are able to traffic between the peripheral circulation and the central nervous system (CNS) in patients with MS, molecular players involved in this migration have not yet been elucidated. In this study, we demonstrated that activated leukocyte cell adhesion molecule (ALCAM/CD166) identifies subsets of proinflammatory B lymphocytes and drives their transmigration across different CNS barriers in mouse and human. We also showcased that blocking ALCAM alleviated disease severity in animals affected by a B cell–dependent form of experimental autoimmune encephalomyelitis. Last, we determined that the proportion of ALCAM+ B lymphocytes was increased in the peripheral blood and within brain lesions of patients with MS. Our findings indicate that restricting access to the CNS by targeting ALCAM on pathogenic B lymphocytes might represent a promising strategy for the development of next-generation B lymphocyte–targeting therapies for the treatment of MS.

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