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The Oncogenic Roles of JC Virus T Antigen in Breast Carcinogenesis.

Purpose: JC virus (JCV) infects 80-90% of the population and results in progressive multifocal leukoencephalopathy upon immunodeficiency. The study aimed to pathologically clarify the oncogenic roles of T antigen in human breast cancers. Methods: Breast cancer, dysplasia, and normal tissues were examined for T antigen of JCV by nested and real-time PCR. The positive rate or copy number of T antigen was compared with clinicopathological parameters of breast cancer. JCV existence was morphologically detected by immunohistochemistry and in situ PCR. T antigen was examined by Western blot using fr…

Smoking is not associated with higher prevalence of JC virus in MS patients.

John Cunningham virus (JCV) causes rare, but potentially life-threatening progressive multifocal leukoencephalopathy (PML) in natalizumab-treated multiple sclerosis (MS) patients. Beside JCV index, there is currently no other factor for further risk stratification. Because smoking was reported as potential risk factor for several viral and bacterial infections, we aimed to investigate whether smoking could increase the risk for JCV infection in MS patients. We screened our database of the MS Clinic of the Department of Neurology, Medical University of Innsbruck, Austria, for patients with know

The effect of plasma exchange on serum anti-JC virus antibodies.

OBJECTIVE: Natalizumab, a highly effective treatment for multiple sclerosis (MS) and Crohn's disease, is associated with progressive multifocal leukoencephalopathy (PML). Upon suspicion or diagnosis of PML, plasma exchange (PLEX) is performed to remove natalizumab from the circulation, allowing immune reconstitution of the central nervous system. Since PLEX may also remove other circulating antibodies, we examined the effects of PLEX on serum immunoglobulin (IgG) and anti-JC virus (JCV) antibody levels in MS patients with and without PML. METHODS: Serum samples from 12 natalizumab-treated pat…

Вариант вируса JC связан с атрофией мозга у больного СПИДом.

Вирус геномавируса человека (JCV) является агентом прогрессивной многофукальной лейкоэнцефалопатии (PML). Она также недавно занималась атрофией головного мозга. Факторы, связанные с этим образованием, являются неясными. Мы представляем случай инфицированного вирусом иммунодефицита человека (ВИЧ) пациента с атрофией PML и мозгового мозга. Помимо разделения штаммов JCV между мочой, цереброспинной жидкостью и мозжечком, в районе регулирования JCV в мозжечке были отмечены конкретные реструктуризации, что привело к изменению связующих участков с коэффициентом транскрипции. Наши данные свидетельству

Совпадение в аннотации оригинала
The human polyomavirus JC virus (JCV) is the agent of progressive multifocal leukoencephalopathy (PML). It has also recently been involved in cerebellar atrophy. Factors involved in this entity are elusive. We present a case of a human immunodeficiency virus (HIV)-infected patient with PML and cerebellar atrophy. In addition to a compartmentalization of JCV …

Identification and characterization of mefloquine efficacy against JC virus in vitro.

Progressive multifocal leukoencephalopathy (PML) is a rare but frequently fatal disease caused by the uncontrolled replication of JC virus (JCV), a polyomavirus, in the brains of some immunocompromised individuals. Currently, no effective antiviral treatment for this disease has been identified. As a first step in the identification of such therapy, we screened the Spectrum collection of 2,000 approved drugs and biologically active molecules for their anti-JCV activities in an in vitro infection assay. We identified a number of different drugs and compounds that had significant anti-JCV activi…

Reactivation of JC virus and development of PML in patients with multiple sclerosis.

The attention of researchers and clinicians specializing in both multiple sclerosis (MS) and JC virus (JCV), the etiologic agent of progressive multifocal leukoencephalopathy (PML), was rekindled by the development of PML in two patients with MS enrolled in a clinical trial of combination therapy with natalizumab (Tysabri) and interferon beta-1A (Avonex) in recent years. PML had not been previously reported with either MS or treatment with interferon beta alone. This occurrence of PML with alpha4beta1-integrin inhibition in MS raised a number of issues in terms both of the scientific understan…

Detection of JC virus DNA sequences in colorectal cancers in Japan.

JC virus (JCV), a ubiquitous polyoma virus that commonly infects humans, was first identified as the etiologic agent for the fetal demyelinating disease, progressive multifocal leukoencephalopathy. Recently, a number of reports have documented detection of JCV in samples derived from several types of neural as well as non-neural human tumors. It has been suggested that oncogenicity of JCV depends on a T antigen having a strict structural homology to the T antigen of simian virus 40. To clarify whether JCV might have a potential role with regard to colorectal cancers, we investigated the presen…

Advances in the biology of JC virus and induction of progressive multifocal leukoencephalopathy.

Since the initial description of progressive multifocal leukoencephalopathy (PML) in 1958, clinical and basic science investigators have demonstrated a growing interest in the area of neurovirology, with a recent focus on polyomaviruses. In this review, the authors present an overview of the biological properties of the human polyomavirus, JC virus (JCV), and its association with PML as the etiologic agent. Additionally, the authors provide a discussion of the current understanding of JCV molecular pathogenesis and therapeutic strategies.

Progressive myoclonic ataxia and JC virus encephalitis in an AIDS patient.

A case of progressive myoclonic ataxia in an AIDS patient is described, which evolved over a 13 month period. The ataxia persisted as the only clinical finding for several months before the appearance of a severe tetraparesis and cachexia. Throughout the clinical progression, magnetic resonance imaging (MRI) revealed the presence of bilateral, progressive, isolated, and symmetrical lesions involving the red nuclei, subthalami, thalami, lenticular nuclei, and primary motor cortices. Neuropathological examination, supplemented by in situ hybridisation for JC virus DNA, confirmed that the lesions…

Transcriptional regulation of the glial cell-specific JC virus by p53.

The human polyomavirus JC virus is the etiologic agent of progressive multifocal leukoencephalopathy (PML). As the JC virus early promoter directs cell-specific expression of the viral replication factor large T antigen, transcriptional regulation constitutes a major mechanism of glial tropism in PML. It has been demonstrated that SV40 or JC virus large T antigen interacts with p53 protein and regulates many viral and cellular genes. In this study we found that p53 represses the JC virus early promoter in both glial and nonglial cells. To identify the cis-regulatory elements responsible for p5…

[Advances in the diagnosis and treatment of infections caused by herpesvirus and JC virus].

During the last two years important advances in the diagnosis and treatment of cytomegalovirus (CMV) disease have occurred. Several studies … to allow the diagnosis of progressive multifocal leukoencephalopathy (PML) based on the finding of JC virus DNA in CSF by PCR. There are still no drugs with proven clinical efficacy against JC virus but the possibility that HAART treatments might improve the control of this disease appear promising.

Implications of progressive multifocal leukoencephalopathy and JC virus for the etiology of MS.

JCV infects oligodendrocytes and, to a lesser extent, astrocytes in the brain and spinal cord and causes the demyelinating disease known as progressive multifocal leukoencephalopathy (PML) in immunocompromised individuals. The possibility exists that this opportunistic infection reactivates from a latent state in the brain. It is proposed that the pathogenetic immune response in a multiple sclerosis (MS) brain may be directed predominantly toward antigens of a DNA virus, such as JCV, which is latent in glial cells. The target antigens could be synthesized only during transient viral reactivati

Naturally occurring and passage-induced variation in the genome of JC virus.

We have examined both the naturally occurring and passage-induced variation in the genome of the human polyomavirus, JCV. JCV DNA was extracted directly from diseased brain tissue of ten cases of progressive multifocal leukoencephalopathy (PML) and the DNA population from any one case was homogeneous with respect to length and restriction endonuclease cleavage patterns. However, a comparison of cloned JCV DNAs revealed that the viral DNAs derived from different cases of PML were not identical. We identified a hypervariable region near the origin of DNA replication, and we demonstrated that the

Detection of BK virus and JC virus in urine and brain tissue by the polymerase chain reaction.

DNAs of the human polyomaviruses BK virus (BKV) and JC virus (JCV) were amplified by the polymerase chain reaction (PCR) by using a single pair of 20-base oligonucleotide primers that were complementary to the same regions of both viruses. The sequences flanked by the primers were unique for each virus and could be differentiated by hybridization with 40-base, 32P-labeled oligonucleotide probes or by cleavage with BamHI. The DNA fragments resulting from amplification of BKV and JCV were 176 and 173 nucleotide pairs, respectively. The sensitivities of PCR for amplification of cloned BKV and JCV…

Beyond antivirals: virus-specific T-cell immunotherapy for BK virus haemorrhagic cystitis and JC virus progressive multifocal leukoencephalopathy.

PURPOSE OF REVIEW: The clinical manifestations of the polyomaviruses BK and JC in immunocompromised patients include BK virus (BKV) induced haemorrhagic cystitis and nephropathy, and JC virus (JCV) associated progressive multifocal leukoencephalopathy (PML) and are typically a consequence of impaired adaptive immunity in the host. To date, little clinical success has been achieved with antiviral agents or other drug therapies to treat these conditions. Here we review the methods and outcomes of the most recent clinical studies utilising adoptive immunotherapy with BK and/or JC virus-specific T…

JC virus granule cell neuronopathy: A cause of infectious cerebellar degeneration.

JC virus (JCV) infection of glial cells can lead to progressive multifocal leukoencephalopathy (PML) in immunocompromised patients. A newly described phenotype of the infection is infection of neurons. This distinct clinical and radiological syndrome is named JCV granule cell neuronopathy, characterized by exclusive or predominant cerebellar atrophy. We report the clinical and radiological longitudinal findings of 5 HIV-infected patients referred to us between September 2004 and November 2011 who exhibited JCV granule cell neuronopathy (4 probable cases and 1 possible). The association of immu…

Anti-JC virus antibody prevalence in a multinational multiple sclerosis cohort.

JC virus (JCV) is an opportunistic virus known to cause progressive multifocal leukoencephalopathy. Anti-JC virus (Anti-JCV) antibody prevalence in a large, geographically diverse, multi-national multiple sclerosis (MS) cohort was compared in a cross-sectional study. Overall, anti-JCV antibody prevalence was 57.6%. Anti-JCV antibody prevalence in MS patients ranged from approximately 47% to 68% across these countries: Norway, 47.4%; Denmark, 52.6%; Israel, 56.6%; France, 57.6%; Italy, 58.3%; Sweden, 59.0%; Germany, 59.1%; Austria, 66.7% and Turkey, 67.7%. Prevalence increased with age (from 49…

Safety, anxiety and natalizumab continuation in JC virus-seropositive MS patients.

The use of natalizumab in multiple sclerosis has been restricted by the risk of progressive multifocal leukoencephalopathy (PML). JC virus carriership, duration of natalizumab treatment and past immunosuppression are known risk factors. This has allowed for calculated risk assessment for individual patients to be implemented. Not much data are available about the effect of JCV carriership on patient willingness to continue natalizumab. Here, we evaluated the impact of JCV seropositivity on safety feelings, anxiety and treatment continuation for patients treated with natalizumab, using a visual…

JC virus granule cell neuronopathy and GCN-IRIS under natalizumab treatment.

Progressive multifocal leukoencephalopathy is the most common clinical presentation of JC virus (JCV)-associated central nervous system (CNS) disease and has emerged as a major safety concern in multiple sclerosis patients treated with the monoclonal antibody natalizumab. Here we report clinical, radiological, and histological findings of a case of cerebellar granule cell neuronopathy (GCN), a JCV-associated CNS disease, so far unreported amongst patients treated with natalizumab. GCN should be considered as a JCV CNS manifestation in patients with newly developed, progressive cerebellar signs…

Inhibitory interactions between BK and JC virus among kidney transplant recipients.

BK and JC polyomaviruses can reactivate after transplantation, causing renal dysfunction and graft loss. The incidence of JC reactivation after renal transplant is not well understood. Here, we characterized JC reactivation using samples collected during the first year after transplantation from 200 kidney recipients. We detected BK and JC viruses in the urine of 35 and 16% of transplant recipients, respectively. The median viral load in the urine was 400 times higher for BK virus than JC virus. The presence of BK viruria made concurrent JC viruria less likely: JC viruria was detected in 22% o…