Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “JC Virus”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources
PubMed1999

BK and JC viruses in patients with systemic lupus erythematosus: prevalent and persistent BK viruria, sequence stability of the viral regulatory regions, and nondetectable viremia.

A role for polyomaviruses in the pathogenesis of systemic lupus erythematosus (SLE) has been suggested. BK virus (BKV) and JC virus (JCV) were demonstrated in single urine specimens from 7 (16%) of 44 and 5 (11%) of 44 patients with SLE and 0/88 and 18 (21%) of 88 matched healthy controls, respectively. During a 1-year follow-up study, episodes of polyomaviruria were detected in 16 (80%) of 20 patients, BKV in 13, and JCV in 3 patients. A group of 12 (60%) of 20 patients demonstrated persistent or recurrent polyomaviruria, BKV viruria (n=9), or JCV viruria (n=3) in 180 (70%) of 256 specimens. Polyomaviruria was not significantly associated with immunosuppressive therapy. The BKV and JCV isolates revealed predominantly stable archetypal regulatory regions over 3 years, indicating viral persistence rather than reinfection as a cause for urinary shedding. The demonstration of nondetectable viremia and stable archetypal BKV and JCV noncoding control regions during persistent viruria argue against the urinary tract as a focus for the creation of rearranged regulatory region variants.

Adult↗
PubMed2006

Irisolidone, an isoflavone metabolite, represses JC virus gene expression via inhibition of Sp1 binding in human glial cells.

Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease that results from an oligodendrocyte infection caused by the JC virus. Therefore, inhibiting the expression of JC virus is important for preventing and/or treating PML. This study found that irisolidone, an isoflavone metabolite, significantly inhibited the JC virus expression in primary cultured human astrocytes and glial cell lines. Studies examining the underlying mechanism revealed that a mutation of the Sp1 binding site downstream of the TATA box (Sp1-II) dramatically diminished the inhibitory activity of irisolidone. In addition, an irisolidone treatment repressed Sp1 binding to Sp1-II site, which is important for the basal JC virus promoter activity. The results suggest that the inhibitory effect of irisolidone against the JC virus may be attributed at least in part to the suppression of Sp1 binding to the JC virus promoter region. Therefore, the inhibition of the JC virus expression by irisolidone might provide therapeutic potential for PML caused by the JC virus.

Base Sequence↗
PubMed1992

[BK and JC viruses--2 polyomaviruses causing disease in immunosuppressed patients].

BK and JC viruses are two polyoma viruses designated by the initials of the patients from whom they were first isolated. After the primary infection, usually occurring in childhood or early school age, the viruses become latent. Reactivation occurs during immunosuppression, and the BK virus has been shown to be the main cause of viral hemorrhagic cystitis in bone marrow transplanted patients, while the JC virus has been found to cause progressive multifocal leukoencephalopathy, PML. The paper consists in a report of results obtained with an established method for the amplification of BK and JC virus DNA. Of 20 urine specimens from patients with hemorrhagic cystitis, 13 were found to be BK virus-positive. Post-transplantation follow-up shows that the virus continues to remain detectable for long periods. JC virus positivity was found in central nervous system material (a cerebrospinal spinal fluid specimen in one case) from two PML patients.

BK Virus↗
PubMed2002

Expression of JC virus T-antigen in a patient with MS and glioblastoma multiforme.

OBJECTIVE: To investigate the presence of human polyomavirus JC virus genome and the expression of the viral oncoprotein T-antigen in neoplastic cells of a patient with MS and a glioblastoma multiforme. BACKGROUND: The postmortem examination of an immunocompetent patient with a neurologic disorder revealed the concurrence of MS plaques in the white matter of the brain and a glioblastoma multiforme in the region of the thalamus. METHODS AND RESULTS: PCR analysis of DNA from demyelinated plaques and the tumor area using primers derived from specific regions of the JC virus genome revealed the presence of viral DNA corresponding to the viral early and late genes. Further examination of the samples for the JC virus regulatory region identified the presence of sequences identical to JC virus Mad-4 and JC virus W1 viral isolates in the tumor and the demyelinated regions. Results from immunohistochemistry showed the detection of the viral early protein, T-antigen, and the cellular tumor suppressor protein, p53, in the nuclei of neoplastic cells. Interestingly, expression of T-antigen, but not p53, was observed in neurofilament-positive cells with neuronal morphology and in glial fibrillary acidic protein-positive astrocytes in the cortex juxtaposed to the MS plaques. Examination of viral late gene expression by immunohistochemistry showed no evidence for viral capsid proteins, thus ruling out productive replication of JC virus in the tumor and MS demyelinated plaques. CONCLUSIONS: These observations provide molecular and clinical evidence of the association of JC virus in the brain of a patient with concurrent glioblastoma multiforme and MS.

Aged↗
PubMed1998

An association, in adult Japanese, between the occurrence of rogue cells among cultured lymphocytes (JC virus activity) and the frequency of "simple" chromosomal damage among the lymphocytes of persons exhibiting these rogue cells.

Data from a previous study of the cytogenetic effects, in cultured lymphocytes, of exposure to the atomic bomb in Hiroshima have been reanalyzed to determine the relationship between the occurrence of "rogue" cells in an individual and the frequency of "simple" chromosomal damage in the nonrogue cells of the same individual. Rogue cells are cells with complex chromosomal damage, currently believed to be a manifestation of the activity of a human polyoma virus termed "JC." Among a total of 1,835 persons examined, there were 45 exhibiting rogue cells. A total of 179,599 cells were scored for simple chromosomal damage. In both the exposed and the control populations, there was an absolute increase of approximately 1.5% in the frequency of simple chromosomal damage in the nonrogue cells of those exhibiting rogue cells, when compared with the frequencies observed in those not exhibiting rogue cells, which is a statistically significant difference. It is argued that this phenomenon, occurring not only in lymphocytes but possibly also in other cells/tissues, may play a contributory role in the origin of malignancies characterized by clonal chromosome abnormalities. Unexpectedly, among those exhibiting rogue cells, there was a disproportionately greater representation of persons who had received relatively high radiation exposures from the bomb. The reason for this is unclear, but it is tempting to relate the finding to some lingering effect of the exposure (or the circumstances surrounding the exposure) on immunocompetence.

Adult↗
PubMed2004

Internalization of exogenous human immunodeficiency virus-1 protein, Tat, by KG-1 oligodendroglioma cells followed by stimulation of DNA replication initiated at the JC virus origin.

JC virus (JCV) is the etiological agent of an opportunistic brain infection, progressive multifocal leukoencephalopathy (PML), in AIDS. PML is fatal in approximately 4% of HIV-infected individuals, and although the overall incidence has fallen due to highly aggressive antiretroviral therapy (HAART), this percent has remained steady. It has been shown that the Tat protein of human immunodeficiency virus-1 (HIV-1) interacts in cells with cellular protein Puralpha. This interaction can stimulate transcription of both HIV-1 and JCV genes. HIV-1, however, infects primarily microglia and astrocytes in the brain, whereas JCV infects primarily oligodendrocytes. Although HIV-1 has been shown capable of infecting oligodendrocytes in vitro (Albright et al., 1996), no instance of viral coinfection of such cells with JCV has been reported. Tat is known to be secreted from cells in which it is made. Here we ask whether such exogenous Tat can influence JCV replication in oligodendrocytes. We find that glial cells infected with either HIV-1 or JCV are in proximity at the outer edge of PML lesions. Exogenous Tat is avidly incorporated into cultured KG-1 oligodendroglioma cells over a 72-h period and is colocalized with endogenous Puralpha both nuclear and juxtanuclear. At concentrations in the medium well below the pM range, Tat stimulates several-fold the replication in vivo of DNA initiated at the JCV origin. These results define a pathway by which a protein made by HIV-1 can directly affect the course of infection by another disease-causing virus.

Cell Line, Tumor↗
PubMed1977

JC virus, a human polyomavirus associated with progressive multifocal leukoencephalopathy: additional biological characteristics and antigenic relationships.

JC virus, a human polyomavirus, failed to grow or produce cytopathic effects in any of a variety of cells tested other than primary human fetal glial (PHFG) cells. Cells tested included other primary human cells and glial cells from other animals. Only a rare cell in inoculated insusceptible human cell cultures produced T or virion antigen. In PHFG cell cultures JC virus produced subtle cytopathic effects, and the majority of progeny remained cell associated. Only a few cells in the heterogenous PHFG cell cultures contained T antigen at 24 h postinoculation, and virion antigen was not detected until 48 h postinoculation. The infectivity of JC virus was resistant to inactivation by ether and by heating at 50 degrees C for 1 h. A three-way minor antigenic relationship was demonstrated among the virion antigens of JC virus, BK virus, and simian virus 40 by neurtralization and/or hemagglutination inhibition tests. Serological evidence is presented for the existence of JC virus as a distinct entity before the use of simian virus 40-contaminated poliovirus vaccines and for the nonexistence of an animal reservoir for JC virus infection.

Animals↗
PubMed1993

Detection of reactivation and size variation in the regulatory region of JC virus in brain tissue.

AIMS: To develop a sensitive and specific polymerase chain reaction (PCR) based system for detecting genomic variation in JC virus. To apply this system to formalin fixed, paraffin wax embedded brain tissue from patients with and without progressive multifocal leucoencephalopathy (PML). METHODS: A pair of primers (JC1 and JC2) were designed to be complementary to the early and late regions of JC and BK polyomaviruses, respectively. A third primer (JC3), internal to JC1 and JC2, was designed to be specific for JC virus. The specificity of JC3 was investigated by amplifying plasmids with BK or JC virus genomes. Sensitivity was estimated by titration of a plasmid containing JC virus genome. Seven brains from patients with PML (PMLB) and 30 from patients without PML (non-PMLB) were amplified using JC1 and JC2, followed by JC1 and JC3. Amplification of the beta globin gene was used as an amplification control. RESULTS: Amplification with JC1 and JC2 was common for JC and BK viruses, but with JC1 and JC3 it was specific for JC virus. The sensitivity of the system was 25 copies of JC plasmid per 10 microliters of digested tissue. Five out of seven PMLB and 28 of the 30 non-PMLB amplified for beta globin, but only the PMLB gave a signal with polyoma primers. Hypervariation of the length of the regulatory region of the JC isolates in the PML tissues was consistent with the presence of multiple strains of JC. CONCLUSIONS: Variation in the regulatory region of JC virus can be specifically and sensitively detected from routinely processed, paraffin wax embedded brain tissue. Variation in the regulatory region is common in PML derived JC strains, but JC virus was not detectable in non-PMLB tissue.

Adult↗
PubMed1996

Activation of the JC virus Tat-responsive transcriptional control element by association of the Tat protein of human immunodeficiency virus 1 with cellular protein Pur alpha.

JC virus is activated to replicate in glial cells of many AIDS patients with neurological disorders. In human glial cells, the human immunodeficiency virus 1 (HIV-1) Tat protein activates the major late promoter of JC virus through a Tat-responsive DNA element, termed upTAR, which is a recognition site for cellular Pur alpha, a sequence-specific single-stranded DNA binding protein implicated in cell cycle control of DNA replication and transcription. Tat interacts with two leucine-rich repeats in Pur alpha to form a complex that can be immunoprecipitated from cell extracts. Tat enhances the ability of purified glutathione S-transferase-Pur alpha (GST-Pur alpha) to bind the upTAR element. Tat acts synergistically with Pur alpha, in a cell-cycle-dependent manner, to activate transcription at an upTAR element placed upstream of a heterologous promoter. Since Pur alpha is ubiquitously expressed in human cells and since PUR elements are located near many promoters and origins of replication, the Tat-Pur alpha interaction may be implicated in effects of HIV-1 throughout the full range of HIV-1-infected cells.

Amino Acid Sequence↗
PubMed1991

Typing of human polyomavirus JC virus on the basis of restriction fragment length polymorphisms.

JC virus DNA clones from the urine of nonimmunosuppressed Japanese individuals regularly contain an archetypal regulatory sequence which may have generated various regulatory sequences of JC virus isolates from patients with progressive multifocal leukoencephalopathy (PML). In this study, we established 15 new clones from the urine of Dutch, German, and Taiwanese healthy volunteers and patients. Most of these clones contained regulatory sequences essentially identical to the archetypal regulatory sequence. These clones, along with two representative urine-derived clones in Japan and five clones from the brains of PML patients (four established in the United States and one established in Japan), were analyzed with a number of restriction enzymes. We found nine restriction fragment length polymorphisms by which all clones were classified into either of the two types, A and B. Type A contained only clones from the West, while type B contained some from the West and all from eastern Asia. Each type contained both urine-derived and PML-derived clones. Furthermore, there was a close relationship between some urine-derived clones and some PML-derived clones in restriction site mapping analysis. These findings support the adaptation hypothesis which has been postulated to explain the genesis of PML-type JC viruses.

Base Sequence↗
PubMedDate not supplied

Systemic infection by JC virus in non-HIV induced immunodeficiency without progressive multifocal leukoencephalopathy.

Reactivation of latent JC virus in immunodeficient subjects can lead to a demyelinating disease following lytic oligodendrocyte infection. It is known as idiopathic CD4+ lymphocytopenia and rarely occurs in immunosuppressed patients who are not infected by HIV. We describe a case of persistent idiopathic CD4+ lymphocytopenia in an HIV-negative 65-year-old woman. At autopsy, polymerase chain reaction analysis evidenced JC virus DNA in kidney, brain and liver although there were no signs of progressive multifocal leukoencephalopathy or evidence of oligodendrocyte infection. While her disease was not HIV-induced, it closely resembled AIDS in terms of the nature of the immune derangement and the clinical picture. The case also evidences the reactivation of JC virus infection in non-HIV-related immunosuppression in cerebral and/or extracerebral sites: liver infection seems to be particularly relevant since it has not yet been recognized as a common target of JC virus infection or a source of virus spreading. The absence of any sign of progressive multifocal leukoencephalopathy was remarkable: histological examination failed to disclose demyelination or other progressive multifocal leukoencephalopathy changes, and the search for JC virus DNA with in situ methods also gave negative results. The lack of lytic brain infection in this case would seem to support the hypothesis that the expression of progressive multifocal leukoencephalopathy is directly dependent on the presence of HIV infection.

Aged↗
PubMed1991

Sequence rearrangement in JC virus DNAs molecularly cloned from immunosuppressed renal transplant patients.

From nonimmunocompromised individuals, we have recently identified a possible archetypal JC virus DNA sequence from which various regulatory sequences of JC virus isolates derived from patients with progressive multifocal leukoencephalopathy (PML) could have evolved. In this study, we analyzed the regulatory sequences of JCV DNAs cloned from urine samples of a PML risk group (renal transplant patients on immunosuppressive therapy). A number of JC virus DNAs were molecularly cloned from virions excreted in the urine of eight patients. Furthermore, fragments containing the regulatory region were amplified by the polymerase chain reaction and subsequently molecularly cloned from cell-associated JC virus excreted in the urine of two patients. The regulatory regions in all clones were analyzed with restriction enzymes, and those in representative clones were sequenced. We found that clones with the archetypal regulatory sequence were predominant in all urine samples, but a few clones carried regulatory sequences that diverged from the archetypal sequence by deletion or duplication. The finding that sequence rearrangement in the archetypal regulatory region occurs in the course of infection in immunosuppressed hosts is consistent with the adaptation hypothesis which has been put forward to explain the divergence of the regulatory regions in PML-derived JC virus isolates.

Base Sequence↗
PubMed2004

Transcriptional activation of JC virus early promoter by phorbol ester and interleukin-1beta: critical role of nuclear factor-1.

JC virus causes the fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML) under immunosuppressive states such as AIDS. During the pathogenesis of AIDS, HIV-infected microglia secrete cytokines including interleukin-1 and tumor necrosis factor-alpha (TNF-alpha), which affect neuronal cells resulting in dysfunction of the CNS. We hypothesized that extracellular stimuli released from HIV-infected microglia may reactivate JC virus by affecting neighboring oligodendrocytes. In the present study, we found that phorbol myristate acetate (PMA) and interleukin-1beta (IL-1beta) dramatically increased JC virus transcription in glial cells. Site-directed mutagenesis and gel shift analyses revealed that PMA and IL-1beta strongly induced nuclear factor-1 (NF-1) binding to the JC virus enhancer region, increasing transcriptional activity of the viral early promoter. Additionally, we demonstrated that protein kinase C (PKC) pathways were involved in the PMA/IL-1beta-mediated up-regulation of the JC virus early promoter. These findings may represent one of the possible mechanisms for higher incidence of PML among AIDS patients.

Base Sequence↗
PubMed1977

Specificity of the Tumor-specific transplantation antigen induced by JC virus, a human polyomavirus.

The specificity of the tumor-specific transplantation antigen (TSTA) induced by JC virus was investigated by cross protection tests in weanling hamsters. Hamsters immunized with JC virus, BK virus, or SV40 were challenged 5 weeks later with known numbers of JC virus- or SV40-induced hamster tumor cells. Both the JC virus-immune and the SV40-immune hamsters showed resistance to challenge with homologous but not heterologous tumor cells, and the BK virus-immune hamsters were not resistant to either heterologous tumor cell. The TSTA induced by JC virus did not cross-react with that induced by SV40.

Animals↗
PubMed1997

Latency and reactivation of JC virus in peripheral blood of human immunodeficiency virus type 1-infected patients.

JC virus (JCV) acts as an opportunistic virus in immunocompromised human immunodeficiency virus type 1 (HIV-1)-infected patients. The role of peripheral blood cells in central nervous system invasion, before the onset of progressive multifocal leukoencephalopathy (PML), remains controversial. In order to clarify JCV latency or reactivation status in peripheral blood, 72 HIV-1-infected patients were studied, together with 7 HIV-1-positive PML patients and 50 blood donors. Blood leukocytes, plasma, and B lymphocytes were investigated by two complementary DNA amplification procedures within the early T and late VP1 JCV genes and two reverse transcription techniques for the detection of corresponding early transcripts and mRNAs. JCV DNA was detected in 40.3% of the HIV-1-infected patients but only 8% of the blood donors (P < 0.001). Leukocytes represented 82.7% of the positive samples, but plasma from 12 patients (41.4%) contained JCV DNA. B lymphocytes seemed to be involved in the natural history of JCV but did not represent the unique cell target. JCV DNA was intermittently found in blood, and JCV mRNAs for VP1 capsid protein were detected exclusively in one PML patient. Such observations demonstrate that JCV, when detected in blood, does not undergo active multiplication. They support the JCV hematogenous spread hypothesis, but do not indicate any direct link between peripheral virus and dissemination in the central nervous system at the time of immunodepression.

AIDS-Related Opportunistic Infections↗
PubMed1997

Review: JC virus infection of lymphocytes--revisited.

JC virus (JCV), the causative agent of the fatal human demyelinating disease progressive multifocal leukoencephalopathy (PML), is an opportunistic papovavirus that infects and destroys oligodendrocytes, the myelin-producing cells of the central nervous system. Since its isolation from the brain of a PML patient, JCV has long been classed as a neurotropic virus. Many studies, however, have demonstrated that JCV can infect various other cell types, including immune system cells. Moreover, several recent studies have focused specifically on lymphocytes as a target of JCV. This review chronicles the association of JCV with lymphocytes, including cell type localization, molecular regulation, and viral sequences, and discusses clinical implications of these findings.

Antigens, Viral↗
PubMed2003

An overview: Human polyomavirus JC virus and its associated disorders.

JC virus (JCV) is a polyomavirus infecting greater than 80% of the human population early in life. Replication of this virus in oligodendrocytes and astrocytes results in the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML) in immunocompromised individuals, most notably acquired immunodeficiency syndrome (AIDS) patients. Moreover, recent studies have pointed to the association of JCV with a variety of brain tumors, including medulloblastoma. The JCV genome encodes for viral early protein, including large and small T antigens and the newly discovered isoform T', at the early phase of infection and the structural proteins VP1, VP2, and VP3 at the late stage of the lytic cycle. In addition, the late gene is responsible for the production of a small nonstructural protein, agnoprotein, whose function is not fully understood. Here, we have summarized some aspects of the JCV genome structure and function, and its associated diseases, including PML and brain tumors.

Humans↗
PubMed1991

Human fetal Schwann cells support JC virus multiplication.

The human papovavirus JC virus (JCV), the etiologic agent of progressive multifocal leukoencephalopathy, displays a narrow host range for growth, preferentially infecting oligodendrocytes, the myelin-producing cells of the central nervous system. In tissue culture, human fetal brain cells have been used for JCV propagation because of their ability to support JCV virion production. In this study, we evidence that a human fetal cell type derived from the peripheral nervous system can be productively infected with JCV. Schwann cells, the cell type responsible for myelination in the peripheral nervous system, support the expression of JCV T antigen and JCV DNA replication. However, viral proteins and DNA replication were not detected either in dorsal root ganglion neurons or fibroblasts. These results extend the host range of JCV to include another cell of the glial lineage whose function is myelin formation.

Antigens, Viral↗