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Viruses Sep 2021Polyomavirus JC (JCPyV) causes the demyelinating disease progressive multifocal leukoencephalopathy (PML). JCPyV infection is very common in childhood and, under...
Polyomavirus JC (JCPyV) causes the demyelinating disease progressive multifocal leukoencephalopathy (PML). JCPyV infection is very common in childhood and, under conditions of severe immunosuppression, JCPyV may reactivate to cause PML. JC viral proteins expression is regulated by the JCPyV non-coding control region (NCCR), which contains binding sites for cellular transcriptional factors which regulate JCPyV transcription. Our earlier studies suggest that JCPyV reactivation occurs within glial cells due to cytokines such as TNF-α which stimulate viral gene expression. In this study, we examined interferon-α (IFNα) or β (IFNβ) which have a negative effect on JCPyV transcriptional regulation. We also showed that these interferons induce the endogenous liver inhibitory protein (LIP), an isoform of CAAT/enhancer binding protein beta (C/EBPβ). Treatment of glial cell line with interferons increases the endogenous level of C/EBPβ-LIP. Furthermore, we showed that the negative regulatory role of the interferons in JCPyV early and late transcription and viral replication is more pronounced in the presence of C/EBPβ-LIP. Knockdown of C/EBPβ-LIP by shRNA reverse the inhibitory effect on JCPyV viral replication. Therefore, IFNα and IFNβ negatively regulate JCPyV through induction of C/EBPβ-LIP, which together with other cellular transcriptional factors may control the balance between JCPyV latency and activation.
Topics: CCAAT-Enhancer-Binding Protein-beta; Cell Line, Tumor; DNA, Viral; Gene Expression; Gene Expression Regulation, Viral; Humans; Interferon-alpha; Interferon-beta; JC Virus; Leukoencephalopathy, Progressive Multifocal; Neuroglia; Protein Isoforms; Virus Replication
PubMed: 34696366
DOI: 10.3390/v13101937 -
Journal of the National Cancer Institute Feb 2002
Topics: Brain Neoplasms; Genes, p53; Humans; JC Virus; Medulloblastoma
PubMed: 11854380
DOI: 10.1093/jnci/94.4.240 -
Epidemiology and Health 2018John Cunningham virus (JCV) is a polyoma virus that infects humans, mainly in childhood or adolescence, and presents no symptomatic manifestations. JCV can cause... (Review)
Review
OBJECTIVES
John Cunningham virus (JCV) is a polyoma virus that infects humans, mainly in childhood or adolescence, and presents no symptomatic manifestations. JCV can cause progressive multifocal leukoencephalopathy (PML) in immunosuppressed individuals, including those undergoing treatment for multiple sclerosis (MS) and neuromyelitis optica (NMO). PML is a severe and potentially fatal disease of the brain. The prevalence of JCV antibodies in human serum has been reported to be between 50.0 and 90.0%. The aim of the present study was to review worldwide data on populations of patients with MS and NMO in order to establish the rates of JCV seropositivity in these individuals.
METHODS
The present review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and used the following search terms: "JCV" OR "JC virus" AND "multiple sclerosis" OR "MS" OR "NMO" OR "neuromyelitis optica" AND "prevalence." These terms were searched for both in smaller and in larger clusters of words. The databases searched included PubMed, MEDLINE, SciELO, LILACS, Google Scholar, and Embase.
RESULTS
After the initial selection, 18 papers were included in the review. These articles reported the prevalence of JCV antibodies in the serum of patients with MS or NMO living in 26 countries. The systematic review identified data on 29,319 patients with MS/NMO and found that 57.1% of them (16,730 individuals) were seropositive for the anti-JCV antibody (range, 40.0 to 69.0%).
CONCLUSIONS
The median worldwide prevalence of JCV among adults with MS or NMO was found to be 57.1%.
Topics: Antibodies, Viral; Global Health; Humans; JC Virus; Multiple Sclerosis; Neuromyelitis Optica; Prevalence
PubMed: 29370683
DOI: 10.4178/epih.e2018001 -
Journal of Cellular Physiology Aug 2010Although the remarkable efficacy of biological therapy has resulted in significant success in inflammatory bowel disease (IBD) management, susceptibility to infections... (Review)
Review
Although the remarkable efficacy of biological therapy has resulted in significant success in inflammatory bowel disease (IBD) management, susceptibility to infections remains a concern. The biological agents include the tumor necrosis factor-alpha (TNF-alpha) inhibitors, for instance infliximab, and other immunomodulating agents, such as natalizumab. Progressive multifocal leukoencephalopathy (PML), a rare but mostly fatal opportunistic brain infection caused by reactivation of the human polyomavirus JC virus (JCV), has been found in two patients with multiple sclerosis and one patient with Crohn's disease (CD), linked to treatment with natalizumab. After these cases of PML, the commercial and investigational use of natalizumab was suspended in February 2005 but was subsequently resumed for multiple sclerosis and for CD, only through a special restricted distribution program. This review, starting from an extensive literature search by the PubMed database, resumes the clinical aspects and pathophysiology of CD and focuses on the biologics in current use in CD (infliximab, adalimumab, and natalizumab), in order to provide a reference and gateway to prevention, recognition, and management of JCV, in the early years of biological agents therapy. It also proposed to provide an overview on the hypothetical mechanism of reactivation of JC virus related to the use of these drugs.
Topics: Biological Therapy; Crohn Disease; Humans; JC Virus; Models, Biological; Risk Factors; Virus Activation
PubMed: 20432445
DOI: 10.1002/jcp.22146 -
Virus Research Feb 2016The in vitro expression of the Polyomavirus JC (JCPyV) microRNAs, JC-miRNA-3p and -5p, at early time points post-infection was investigated. The expression of the JCPyV...
The in vitro expression of the Polyomavirus JC (JCPyV) microRNAs, JC-miRNA-3p and -5p, at early time points post-infection was investigated. The expression of the JCPyV microRNAs was monitored in hematopoietic progenitor KG-1 cells and in kidney fibroblast-like COS-7 cells transformed with SV40 after infection with a JCPyV CY archetype viral clone. The JCPyV DNA viral load was low in KG-1 cells compared with that in COS-7 cells, which showed productive viral replication. The expression of the JCPyV microRNAs was observed from 12h after the viral infection of both cell types and in the exosomes present in their cell supernatant. Additionally, this study verified that the JCPyV microRNAs in the exosomes present in the supernatants produced by the infected cells might be carried into uninfected cells. These findings suggest that additional investigations of the expression of JCPyV microRNAs and their presence in exosomes are necessary to shed light on their regulatory role during viral reactivation.
Topics: Animals; Cell Line; Chlorocebus aethiops; DNA, Viral; Exosomes; Gene Expression Profiling; Humans; JC Virus; MicroRNAs; RNA, Viral; Time Factors; Viral Load
PubMed: 26763354
DOI: 10.1016/j.virusres.2015.11.026 -
Journal of Clinical Gastroenterology Aug 2010
Topics: Animals; Colorectal Neoplasms; DNA, Viral; Humans; JC Virus; Polyomavirus Infections; Risk Factors
PubMed: 20520564
DOI: 10.1097/MCG.0b013e3181e0084b -
Microbiology Spectrum Dec 2023Progressive multifocal leukoencephalopathy is a crimpling demyelinating disease of the central nervous system caused by JC polyomavirus (JCPyV). Much about JCPyV...
Progressive multifocal leukoencephalopathy is a crimpling demyelinating disease of the central nervous system caused by JC polyomavirus (JCPyV). Much about JCPyV propagation in the brain remains obscure because of a lack of proper animal models to study the virus in the context of the disease, thus hampering efforts toward the development of new antiviral strategies. Here, having established a robust and representative model of JCPyV infection in human-induced pluripotent stem cell-derived astrocytes, we are able to fully characterize the effect of JCPyV on the biology of the cells and show that the proteomic signature observed for JCPyV-infected astrocytes is extended to extracellular vesicles (EVs). These data suggest that astrocyte-derived EVs found in body fluids might serve as a rich source of information relevant to JCPyV infection in the brain, opening avenues toward better understanding the pathogenesis of the virus and, ultimately, the identification of new antiviral targets.
Topics: Animals; Humans; JC Virus; Astrocytes; Proteomics; Polyomavirus Infections; Extracellular Vesicles; Antiviral Agents
PubMed: 37815349
DOI: 10.1128/spectrum.02751-23 -
JC virus can infect human immune and nervous system progenitor cells: implications for pathogenesis.Advances in Experimental Medicine and... 2006Recent advances in stem cell biology have called attention to the role these cells may play in the pathogenesis of systemic and nervous system diseases. Although not... (Review)
Review
Recent advances in stem cell biology have called attention to the role these cells may play in the pathogenesis of systemic and nervous system diseases. Although not capable of indefinite self renewal and pluripotentiality as stem cells are, progenitor cells can give rise to cells of different lineages. It is infection of these differentiated cells that has traditionally been associated with the pathology and symptoms of viral-induced disease. However, neural progenitor cells have been shown, in vitro, to be susceptible to infection by neurotropic viruses such as the human polyomavirus, JCV, and the lentivirus, HIV-1. These progenitor cells, which exist during development as well as in the fully developed adult brain, could therefore be involved in neuropathogenesis. Morever, JCV can also infect progenitor cells of the hematopoietic system, derivatives of which have been implicated in the trafficking of virus from the periphery to the brain. Interestingly, susceptibility to and molecular regulation of JCV infection in hematopoietic cells closely parallels what has been observed in glial cells. The biological interaction between the immune and nervous systems that exists in the dissemination of virus from periphery to nervous system and the susceptibility of both systems to JCV infection provide potential for hematopoietic and neural progenitor cell involvement in JCV pathogenesis.
Topics: B-Lymphocytes; Central Nervous System; Hematopoietic Stem Cells; Humans; Immune System; JC Virus; Polyomavirus Infections
PubMed: 16626042
DOI: 10.1007/0-387-32957-9_19 -
Journal of Immunotherapy (Hagerstown,... Mar 1997A large body of evidence supports the hypothesis that an infectious agent is involved in the etiology of acute lymphoblastic leukemia (ALL) in children in the 2-5-year... (Review)
Review
A large body of evidence supports the hypothesis that an infectious agent is involved in the etiology of acute lymphoblastic leukemia (ALL) in children in the 2-5-year age range. To explain these data, it has been proposed that some cases of pediatric ALL arise as a rare response to a common childhood infection, and that the leukemia-inducing potential of the agent is related to the timing of infection, with a greater leukemogenic effect for later infections compared with those occurring during infancy. An alternative model for the etiology of a subset of childhood ALL is proposed that places the critical infectious event during pregnancy rather than early childhood. In this model, the etiologic agent causes a primary infection in the mother that is transmitted to the fetus, and as a consequence of this in utero infection, the child is at increased risk of developing ALL before the age of 5 years. The characteristics that the causative infectious agent of childhood ALL occurring in the 2-5-year age range should possess include (a) ability to induce genomic instability; (b) specific effects on B lymphocytes and not on T lymphocytes; (c) higher rates of infection in regions with lower socioeconomic status; (d) limited general oncogenic potential; (e) minimal symptoms associated with the primary infection; and (f) ability to cross the placenta and infect the fetus, but not cause severe fetal abnormalities. A candidate virus meeting many of these criteria is the JC virus, a member of the polyomavirus family. Implications of the possible etiologic role of JC virus for some cases of childhood ALL (especially those with hyperdiploid leukemia cells) are discussed.
Topics: Adult; Child; Female; Genome; Humans; JC Virus; Polyomavirus Infections; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pregnancy; Pregnancy Complications, Infectious; Tumor Suppressor Protein p53; Tumor Virus Infections
PubMed: 9087381
DOI: 10.1097/00002371-199703000-00001 -
Parkinsonism & Related Disorders Apr 2023
Topics: Humans; Multiple System Atrophy; JC Virus; alpha-Synuclein; Brain
PubMed: 36935321
DOI: 10.1016/j.parkreldis.2023.105358