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 127 records · Page 7Linked to original sources
PubMed1982

Prevalence rate and age of acquisition of antibodies against JC virus and BK virus in human sera.

A total of 480 serum samples from donors including 384 children up to 10 years of age were examined by the hemagglutination-inhibition (HI) test for the rates of prevalence and age of acquisition of HI antibodies against JC virus and BK virus. Among 136 serum samples from various age groups, there were five (4%) with no detectable antibodies against BK or JC virus, 75 (55%) with antibodies against both viruses, 41 (30.1%) with antibodies against only BK virus and 26 (19%) with antibodies against only JC virus. The prevalence of antibodies against JC and BK viruses was 70.5% and 80.8%, respectively, and the mean HI titers (4 x 2n,n greater than or equal to 1) were 4.90 and 4.30. About 50% of the children had acquired antibodies against BK virus by 3 years of age and against JC virus by 6 years of age. These results indicate that dual latent infections with both viruses are common, although independent infections with either virus are predominant in the human population.

Adolescent↗
PubMed2000

Influence of JC virus coding region genotype on risk of multiple sclerosis and progressive multifocal leukoencephalopathy.

Two features of the biology of JC virus make it a particularly suitable candidate for an agent in MS-like disease: its neurotropic capability targeting glial cells as evidenced in progressive multifocal leukoencephalopathy lesions, and its capacity for latency and persistence as illustrated by its behaviour in the kidney. JC virus is chronically or intermittently excreted in the urine by some 40% of the population. The existence of JC virus in multiple coding-region genotypes provides a unique approach to the study of JC virus-induced neurological disease. We have previously shown that a genotype originating in Asia but also present in Europe and the US, called Type 2B, is more frequently found in PML brain than expected based on its prevalence in urine samples from a control population. In contrast, we find that the excretion of JCV in MS patients is similar in both genotype and frequency to that of control individuals, and appears to be regulated by factors unrelated to those that control CNS disease activity.

Adjuvants, Immunologic↗
PubMed2002

Molecular biology and immunoregulation of human neurotropic JC virus in CNS.

The human polyomavirus, JC virus (JCV), provides an excellent model system to investigate the reciprocal interaction of the immune and nervous systems. Infection with JCV occurs during childhood and the virus remains in the latent state with no apparent clinical symptoms. However, under immunosuppressed conditions, the virus enters the lytic cycle and upon cytolytic destruction of glial cells, causes the fatal demyelinating disease of the central nervous system (CNS), named progressive multifocal leukoencephalopathy (PML). In this short review, we discuss the molecular pathogenesis of PML by highlighting the role of the immune system in modulating JCV gene activation and replication, and the latency/reactivation of this virus upon immunosuppression. Further, due to the higher incidence of PML among AIDS patients, we further elaborate on the cross-talk between JCV and HIV-1 by direct and indirect pathways that lead to enhanced expression of the JCV genome.

Central Nervous System↗
PubMed2004

Stability of JC virus coding sequences in a case of progressive multifocal leukoencephalopathy in which the viral control region was rearranged markedly.

CONTEXT: It is generally accepted that JC virus variants in the brains of patients with progressive multifocal leukoencephalopathy are generated from archetypal strains through sequence rearrangement (deletion and duplication, or deletion alone) in the control region. This change is thought to occur during persistence of JC virus in patients. OBJECTIVE: The present study was performed to ascertain whether amino acid substitution in the viral proteins is involved in the generation and propagation of JCV variants with rearranged control regions. DESIGN: Many complete JC DNA clones were established from brain tissues (cerebellum, occipital lobe, and brainstem) autopsied in a case of progressive multifocal leukoencephalopathy in which multiple distinct control sequences were detected. Control and coding sequences were determined and compared among the JC DNA clones. RESULTS: Twenty-eight control-region and 20 coding sequences of JC virus were compared. Five rearranged control sequences were detected, but they could be classified into 3 groups that shared common structural features. Viral coding sequences were identical among clones with different control regions and among clones derived from different brain regions. CONCLUSION: In the present case, nucleotide substitution in the viral coding regions (and resultant amino acid change in the viral proteins) was involved neither in the genesis of rearranged JC virus variants nor in the proliferation of demyelinated lesions in the brain.

Adolescent↗
PubMed1989

JC virus genomes in progressive multifocal leukoencephalopathy: detection using a sensitive non-radioisotopic in situ hybridization method.

JC virus genomes have been localized in formalin-fixed, paraffin-embedded brain tissues of two cases of known progressive multifocal leukoencephalopathy by in situ hybridization utilizing a biotinylated JC virus DNA probe. A three-stage immunoperoxidase system with gold-silver amplification of the diaminobenzidine substrate was used to visualize biotinylated nucleic acid hybrids. Dot-blot quantification of this visualization system indicates that subpicogramme amounts of biotinylated DNA can be detected. Optimal detection of the virus genomes in the brain tissues required a microwave irradiation step prior to hybridization. JC virus genomes were observed in the nuclei of enlarged oligodendrocytes and of some bizarre astrocytes. No other cell types were found to harbour the genomes.

Brain↗
PubMed2000

BAG-1, a novel Bcl-2-interacting protein, activates expression of human JC virus.

Transcription of the human polyomavirus JC virus (JCV) genome is regulated by cellular proteins and the large tumour (T) antigen. Earlier studies led to the identification of nuclear factor-1 (NF-1)-binding sites in the JCV enhancer by DNase I protection assays of extracts from retinoic acid (RA)-differentiated P19 embryonal carcinoma (EC) cells. In this study, a cDNA clone that encodes a protein capable of binding to the JCV NF-1 sites was isolated from an RA-differentiated EC cell cDNA library. Sequence analysis revealed that the cDNA isolated was identical to the previously described Bcl-2-interacting protein BAG-1 (Bcl-2-associated athano gene-1). Results from RNA studies indicated that BAG-1 is expressed in several cell types. Co-transfection of a recombinant BAG-1 expression plasmid with JCV promoters indicated that BAG-1 stimulates transcription of the JCV(E) promoter and to a lesser extent the JCV(L) promoter. Mutations in the NF-1 sites in the JCV(E) promoter eliminated the activation by BAG-1. Thus, BAG-1 is a novel transcription factor that may play a role in JCV expression.

Amino Acid Sequence↗
PubMed1993

Detection of JC virus by polymerase chain reaction and colorimetric DNA hybridization assay.

A procedure for rapid detection of JC virus (JCV) using the polymerase chain reaction is described. The procedure was tested in eight HIV-1-seropositive patients with progressive multifocal leukoencephalopathy. One-step DNA extraction using a chelating resin was carried out on clinical samples of cerebrospinal fluid (CSF), urine and brain tissue. After amplification, PCR products were detected by a DNA hybridization method. Microplates were coated with a specific probe and hybridized PCR products were revealed by a commercial colorimetric immunoassay. Using this procedure JC virus DNA was detected in all CSF specimens from patients with progressive multifocal leukoencephalopathy. This sensitive and rapid (24 h) procedure could greatly facilitate use of the DNA probe assay for detection of JC virus in clinical laboratories.

Colorimetry↗
PubMed2000

JC virus as a marker of human migration to the Americas.

JC virus is a ubiquitous human polyomavirus present in populations worldwide. Seven genotypes differing in DNA sequence by approximately 1-3% characterize three Old World population groups (African, European and Asian) as well as Oceania. It is possible to follow Old World populations into the New World by the JC virus genotypes they carried. The first population to settle in the Americas, the Native Americans, brought with them type 2A from northeast Asia. European settlers arriving after Columbus carried primarily type 1 and type 4. Africans brought by the slave trade carried type 3 and type 6.

Americas↗
PubMed1999

Progressive multifocal leukoencephalopathy and JC virus genotypes in West African patients with acquired immunodeficiency syndrome: a pathologic and DNA sequence analysis of 4 cases.

OBJECTIVE: Progressive multifocal leukoencephalopathy is caused by polyomavirus JC in immunosuppressed patients. JC virus genotypes are identified by sequence analysis of the viral genome. Despite the prevalence of acquired immunodeficiency syndrome in sub-Saharan Africa, few cases of progressive multifocal leukoencephalopathy have been reported from this region. Here we describe 4 African cases and provide an analysis of viral genotypes. METHODS: Immunohistochemical staining by labeled streptavidin-biotin for capsid protein antigen was performed on all cases. Polymerase chain reaction amplification of viral genomic DNA was followed by direct cycle sequencing. RESULTS: JC virus type 3 was identified in 2 cases, and type 6 was isolated in 1 case. The viral regulatory region from 1 case showed an uncommon rearrangement pattern. CONCLUSIONS: Progressive multifocal leukoencephalopathy in West African patients with acquired immunodeficiency syndrome is caused by African genotypes of JC virus (types 3 and 6). The prevalence of disease in this autopsy series from sub-Saharan Africa (1.5%) was less than has been reported from Europe and the United States (4% to 10%) and may be partly due to biological differences in JC virus genotypes. Further studies will be needed to confirm this observation.

Acquired Immunodeficiency Syndrome↗
PubMed2005

A comparative study of BK and JC virus infections in organ transplant recipients.

JC virus (JCV) rarely causes kidney disease, whereas BK virus (BKV) is a known cause of viral nephropathy. Existing studies on prevalence of JCV in healthy and transplanted subjects have reported only qualitative detection of viral DNA. We used quantitative PCR (qPCR) to assess JC viral load in transplant recipients and non-immunosuppressed controls, and compared JCV loads to BKV loads. JC viruria was seen in 8/23 (34.7%) controls, 23/103 (22.3%) renal, and 10/44 (22.7%) liver transplant patients. No patient developed JC viremia. BK viruria was seen in 2/23 (8.7%) controls, 36/103 (34.9%) renal, and 7/44 (15.9%) liver transplant patients. BK viremia was seen only in the kidney (8/103 = 7.7%) patients. The mean BKV urinary load was higher in kidney compared to liver patients and controls (4.22E + 07 vs. 2.88E + 05 vs. 4.39E + 02 copies/ml), whereas JC viral load was similar for all three patient groups (1.55E + 06 vs. 2.66E + 06 vs. 2.13E + 06 copies/ml). JCV viral loads were surprisingly high in all patient categories studied, but did not result in viremia or viral nephropathy. Although both BKV and JCV are widely latent in patients accepted for transplantation, concurrent reactivation of both viruses was infrequent. BKV viremia was seen in kidney but not liver recipients. The mechanisms underlying these notable phenomena remain to be investigated.

BK Virus↗
PubMed2005

Establishment of an immunoscreening system using recombinant VP1 protein for the isolation of a monoclonal antibody that blocks JC virus infection.

Polyomavirus JC (JCV) infection causes the fatal human demyelinating disease, progressive multifocal leukoencephalopathy. Although the initial interaction of JCV with host cells occurs through direct binding of the major viral capsid protein (VP1) with cell-surface molecules possessing sialic acid, these molecules have not yet been identified. In order to isolate monoclonal antibodies which inhibit attachment of JCV, we established an immunoscreening system using virus-like particles consisting of the VP1. Using this system, among monoclonal antibodies against the cell membrane fraction from JCV-permissive human neuroblastoma IMR-32 cells, we isolated a monoclonal antibody designated as 24D2 that specifically inhibited attachment and infection of JCV to IMR-32 cells. The antibody 24D2 recognized a single molecule of around 60 kDa in molecular weight in the IMR-32 membrane fraction. Immunohistochemical staining with 24D2 demonstrated immunoreactivity in the cell membrane of JCV-permissive cell lines and glial cells of the human brain. These results suggested that the molecule recognized by 24D2 plays a role in JCV infection, and that it might participate as a receptor or a co-receptor in JCV attachment and entry into the cells.

Animals↗
PubMed1986

Early regions of JC virus and BK virus induce distinct and tissue-specific tumors in transgenic mice.

JC virus and BK virus are ubiquitous human viruses that share sequence and structural homology with simian virus 40. To characterize tissue-specific expression of these viruses and to establish model systems for the study of human viral-induced disease, transgenic mice containing early regions of each of the viruses were produced. The viral sequences induced tumors in a distinct and tissue-specific manner that was similar to their tissue tropism in humans. Ten JC virus-containing founder mice were produced, of which 5 survived to maturity. Four of them developed adrenal neuroblastomas, which metastasized to several other tissues. JC virus tumor-antigen RNA was detected at high levels in the tumor tissues and at low levels in the normal tissues of these mice. One of the three BK virus-containing mice was abnormally shaped and died at 2 weeks of age. The other two BK virus-containing mice developed primary hepatocellular carcinomas and renal tumors and died at 8-10 months of age. BK virus tumor-antigen RNA was expressed in tumor tissues of both mice. Since each of the viruses retained the general tissue tropism that it exhibits in humans, these data suggest that transgenic mice harboring human viruses will be useful as animal models for viral-induced diseases.

Animals↗
PubMed1991

Localization of common cytotoxic T lymphocyte recognition epitopes on simian papovavirus SV40 and human papovavirus JC virus T antigens.

Human papovavirus JC virus (JCV) and Simian virus 40 (SV40) tumor or T antigens demonstrate considerable sequence homology which is reflected by antibody cross-reactivity. This similarity raised the possibility that JCV and SV40 T antigen also might contain common cytotoxic T lymphocyte (CTL) recognition epitopes. In this study we identified and mapped such sites on the JCV T antigen. C57Bl/6 cell lines transformed by JCV/SV40 T antigen chimeras were generated and tested for susceptibility to lysis by five H-2b restricted SV40-specific CTL clones: Y-1, Y-2, Y-3, Y-4, and Y-5. These CTL clones recognize specific epitopes within amino acids 205-219 (site I), 220-233 (sites II and III), 369-511 (site IV), and 489-503 (site V) on SV40 T Ag, respectively. The results show that sites I, II, III, and IV (recognized by CTL clones Y-1, Y-2, Y-3, and Y-4, respectively) represent common epitopes on SV40 and JCV T antigens. CTL clone Y-5 failed to recognize JCV T antigen indicating that CTL can discriminate between the two antigenically related T antigens.

Amino Acid Sequence↗
PubMed2000

Comparison of antibody titers determined by hemagglutination inhibition and enzyme immunoassay for JC virus and BK virus.

A comparison of antibody titers to JC virus (JCV) or BK virus (BKV) was made by hemagglutination inhibition (HI) and enzyme immunoassay (EIA) with 114 human plasma samples. Antibody titers to JCV or BKV determined by HI were lower than those determined by EIA. Nevertheless, as HI titers increased so did EIA titers. When antibody data were compared by the Spearman rank correlation test, highly significant correlations were found between HI and EIA titers. Results obtained by plotting EIA antibody titers for JCV against those for BKV generally showed a reciprocal relationship, i.e., samples with high antibody titers to JCV had lower antibody titers to BKV and vice versa. Some samples, however, had antibody titers to both viruses. Of the samples tested, 25.4% (25 of 114) had HI and EIA antibody titers to JCV and BKV which were identical or closely related. This is not the scenario one would expect for cross-reactive epitopes shared by the two viruses, but one suggesting that these samples were from individuals who had experienced infections by both viruses. Adsorption with concentrated JCV or BKV antigen of sera with high antibody titers to both JCV and BKV and testing by JCV and BKV EIA gave results which support this conclusion. Although 52.6% (51 of 97) of the samples from the Japanese population tested had very high antibody titers (>/=40,960) to either JCV or BKV, none of the samples were found by a dot blot immunoassay to have antibodies which cross-reacted with simian virus 40. The results from this study, in agreement with those of others, suggest that humans infected by JCV or BKV produce antibodies to species-specific epitopes on their VP1 capsid protein, which is associated with hemagglutination and cellular binding.

Antibodies, Viral↗
PubMed2006

T-cell responses to peptide fragments of the BK virus T antigen: implications for cross-reactivity of immune response to JC virus.

Infection with BK virus (BKV) induces both humoral and cellular immunity, but the viral antigens of T-antigen (T-ag) stimulating T-cell responses are largely unknown. To identify BKV-specific T cells in healthy individuals, peripheral blood lymphocytes were cultured with autologous dendritic cells (DCs) loaded with BKV lysate and T cells were screened for intracellular gamma interferon production after stimulation with an overlapping 15mer peptide library of the BKV T-ag. Among many immunogenic peptides identified, four T-ag peptides were identified as candidate major histocompatibility complex class I and II T-cell epitopes, restricted to human leukocyte antigen (HLA)-B*0702, -B*08, -DRB1*0301 and -DRB1*0901. Further, a candidate 9mer peptide, LPLMRKAYL, was confirmed to be restricted to HLA-B*0702 and -B*08. Because the polyomaviruses BKV, JC virus (JCV) and Simian virus 40 (SV40) share extensive sequence similarity in the immunogenic proteins T-ag and VP1, it was hypothesized that, in humans, these proteins contain conserved cytotoxic T-lymphocyte (CTL) target epitopes. Four HLA-restricted conserved epitopes of BKV, JCV and SV40 were identified: HLA-B*07, -B*08 and -DRB1*0901 for T-ag and -A*0201 for VP1. T cells cultured in vitro that were specific for one viral antigen recognized other conserved epitopes. CTLs generated from BKV T-ag and VP1 peptide were cytotoxic to DC targets pulsed with either BKV or JCV. Therefore, infection by one of the two viruses (BKV and JCV) could establish cross-immunity against the other. Although cross-cytotoxicity experiments were not performed with SV40, cross-recognition data from conserved antigen epitopes of polyomaviruses suggest strongly that cross-immunity might also exist among the three viruses.

Amino Acid Sequence↗
PubMed2003

JC virus leukoencephalopathy complicating Wegener's granulomatosis.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the brain caused by the JC virus. It occurs in association with immunodepression due, for instance, to a hematological malignancy, HIV infection, or immunosuppressive therapy for an organ transplant or systemic disease. We describe the fourth reported case of PML in a patient receiving immunosuppressants for Wegener's granulomatosis. A 71-year-old woman receiving azathioprine and glucocorticoid therapy experienced onset of right-sided hemiplegia within a few days, became comatose, and died within a few days. MRI of the brain showed a subcortical lesion in the left parietal lobe generating low signal on T1 images and high signal on T2 images. The initial diagnosis was cerebral vasculitis. However, the postmortem examination showed PML. The diagnosis of PML rests on JC virus detection in the cerebrospinal fluid by PCR assay and on demonstration in a brain biopsy of the typical histological pattern with presence of the JC virus within the demyelinated lesions. No specific or effective treatments are available. Immunosuppressant drugs should be discontinued if possible.

Aged↗
PubMed2003

Lytic JC virus infection in the kidneys of AIDS subjects.

Our objective was to investigate the role of the human polyomavirus JC virus as a possible cause of renal damage in AIDS subjects. Histology, immunohistochemistry, and molecular biology were used to evaluate the frequency of viral infection, genotypes, viral status, and the presence of rearrangements or point mutations in specific genomic regions of strains isolated from renal tissue. Formalin-fixed, paraffin-embedded sections of postmortem renal specimens obtained from 111 unselected AIDS patients were stained for routine histology and with anti-SV40 antibody. The immunohistochemically positive specimens were further investigated by means of nested polymerase chain reaction for different polyomavirus genomic regions (large T, transcriptional control region, and viral protein 1). Furthermore, the sequences of transcriptional control region and viral protein 1 were also analyzed. Immunohistochemistry was positive in seven cases (6.3%), four of which showed morphological evidence of viral replication (intranuclear inclusion bodies and/or intratubular cellular casts): in all seven cases, only epithelial tubular cells (with and without inclusion bodies) and cellular casts were stained. The JC virus genome was identified by polymerase chain reaction in five of the seven immunohistochemically positive cases; transcriptional control region and viral protein 1 were amplified in, respectively, three and four cases. Transcriptional control region sequence analysis revealed major rearrangements in all three cases, with duplications of all the transcriptional factor-binding sites, whereas no point mutations were found in the viral protein 1 region, which was characterized as Type 1A in all cases. For the first time in AIDS subjects, this study shows that although rarely, JC virus can replicate in renal tissue. Molecular biology revealed major rearrangements in the transcriptional control region that, together with other unknown factors, could justify the increased pathogenicity of this human polyomavirus.

AIDS-Associated Nephropathy↗