BK virus, JC virus and Simian Virus 40 infection in humans, and association with human tumors.
Explore the source record for details and available documents.
Antigens, Polyomavirus Transforming↗
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.
[Molecular-pathology analysis of regulatory region and transformation in JC virus].
JC virus, an agent that causes a human demyelinating disease, progressive multifocal leukoencephalopathy (PML), is known to induce brain tumors in hamsters. The regulatory region of the virus reported to be implicated in its tissue specificity and to be highly variable among different isolates. In a study of the regulatory region, first we isolated the JC virus genome directly from the brain of a patient with suspected PML. We amplified the regulatory region of the virus by using the polymerase chain reaction, and we compared with three JC viruses which had been isolated previously (MAD-1, MAD-2, and TKY-1). The brain tissue was shown to be infected with JC virus, as confirmed by the presence of viral antigen on immunohistochemical testing and by the demonstration of viral nucleic acids upon in situ hybridization. Southern blot analysis of the regulatory region disclosed that the isolate from our patient, which was designated as NYS-1, was roughly homologous in all three types of JC viruses, with preservation of the constant regions. However, the cut site for PvuII in NYS-1 was different from that in MAD-1 and MAD-2, and a pair of cut sites, for Nco I-PvuII, was unique to TKY-1 and absent in NYS-1; this showed that NYS-1 was a new type of JC virus. Second, we compared the regulatory regions of TKY-1 and its viral DNA integrated in a hamster brain tumor cell line (I-23) induced by TKY-1. We found no great difference between these two genomes.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Is progressive multifocal leukoencephalopathy a chronic disease because of defective interfering particles or temperature-sensitive mutants of JC virus?
JC virus was examined for temperature sensitivity and for evidence of defective interfering particles as a means of explaining the slow chronic nature of progressive multifocal leukoencephalopathy (PML). JC virus direct from the brain tissue of seven persons with PML was not temperature sensitive as indicated by in vitro assay at 37 and 39 degrees C. In fact, more cells contained viral antigen at 39 than at 37 degrees C. The amount of infectious virus also was increased at 39 degrees C. Virions isolated directly from diseased brain tissue had a higher buoyant density than did virus from the same PML patient passaged in culture and containing genomic deletions. In contrast to DNA from culture-passed virus, DNA extracted from virions direct from brain tissue was homogeneous in length. In 13 separate cases examined, the viral DNA direct from the brain was homogeneous although variations in length were noted among DNAs from different cases. Restriction enzyme cleavage patterns identified all as JC virus DNA. It was concluded that neither temperature sensitivity nor DI particles can be used to explain the slow, progressive nature of PML.
Adult↗
Prevalence of human polyoma virus (BK virus and JC virus) infection in patients with chronic renal disease.
BACKGROUND: Polyoma virus infection in renal transplant patients is sometimes critical in graft survival. But, to date, polyoma virus infection or reactivation has not been checked before renal transplantation. The prevalence of polyoma viruses (BK virus and JC virus) was investigated in 45 patients with renal disease who were future candidates as renal graft recipients. METHODS: Because these viruses are excreted in urine, the urine of these 45 patients was analyzed by polymerase chain reaction (PCR). The urine of 37 age-matched normal subjects (control group) was also investigated. RESULTS: In the control group, 13.5% of the normal subjects were positive for BK virus and 24.3% were positive for JC virus. In the patients with renal disease, 33.3% were positive for BK virus and 33.3% were positive for JC virus; the prevalence of BK virus infection was significantly higher than that in the normal subjects. Patients with renal disease with corticosteroid therapy revealed an especially high prevalence of BK virus infection (55.6%), indicating the possibility of viral reactivation by corticosteroid therapy. CONCLUSIONS: More attention should be paid to polyoma virus infection in candidates for renal transplantation with a previous therapeutic history of corticosteroid administration.
Adrenal Cortex Hormones↗
BK virus and JC virus shed during pregnancy have predominantly archetypal regulatory regions.
Twenty-three BK virus and JC virus DNA samples obtained from urine of pregnant women had almost exclusively archetypal transcriptional control regions. Rearrangements characteristic of laboratory strains are apparently not required for reactivation in humans. Unexpectedly, alignment shows that many elements identified previously in the BK virus enhancer are conserved in the JC virus archetype.
BK Virus↗
Role of the environment in the transmission of JC virus.
JC virus is etiologically associated with a fatal demyelinating disease known as PML. JCV produces persistent infections in the kidney and is excreted in the urine of healthy individuals and in the urine of PML patients. The characteristics of the JCV excreted in the environment have been studied by analyzing sewage samples from divergent geographical areas. The intergenic region of JCV strains detected in the sewage of Barcelona (Spain), Umeå (Sweden), Nancy (France), Pretoria (South Africa), Patras (Greece), Cairo (Egypt), Washington, D.C. (USA), and diverse areas of Northern India has been sequenced, and the phylogenetic analysis showed their relationships with JCV strains previously described in urine or clinical samples in these geographic areas. The JCV regulatory region of the JCV DNA detected in sewage presented archetypal or archetypal-like regulatory regions with the exception of one of the twenty clones obtained from a sewage sample of the area of Washington, D.C. that presented a tandem repeated structure. Infectivity studies showed that archetypal JCV present in the urine of a pregnant woman productively infected SVG cells. Also JC viral particles showed considerable stability in sewage at 20 degrees C and in front of treatments with acidic pH and trypsin. The high prevalence of JCV in urine and in sewage and the stability of the viral particles observed suggests that contaminated water, food, and fomites could be the vehicles of JCV transmission through the oral route. Virions partially degraded or noninfectious could be a source of JCV DNA and may represent an additional mechanism of entry of viral genes into cells.
Environment↗
Oligosaccharides as receptors for JC virus.
JC virus (JCV) belongs to the polyomavirus family of double-stranded DNA viruses and in humans causes a demyelinating disease of the central nervous system, progressive multifocal leukoencephalopathy. Its hemagglutination activity and entry into host cells have been reported to depend on an N-linked glycoprotein containing sialic acid. In order to identify the receptors of JCV, we generated virus-like particles (VLP) consisting of major viral capsid protein VP1. We then developed an indirect VLP overlay assay to detect VLP binding to glycoproteins and a panel of glycolipids. We found that VLP bound to sialoglycoproteins, including alpha1-acid glycoprotein, fetuin, and transferrin receptor, and that this binding depended on alpha2-3-linked sialic acids and N-linked sugar chains. Neoglycoproteins were synthesized by using ovalbumin and conjugation with oligosaccharides containing the terminal alpha2-3- or alpha2-6-linked sialic acid or the branched alpha2-6-linked sialic acid. We show that the neoglycoprotein containing the terminal alpha2-6-linked sialic acid had the highest affinity for VLP, inhibited the hemagglutination activity of VLP and JCV, and inhibited the attachment of VLP to cells. We also demonstrate that VLP bound to specific glycolipids, such as lactosylceramide, and gangliosides, including GM3, GD2, GD3, GD1b, GT1b, and GQ1b, and that VLP bound weakly to GD1a but did not bind to GM1a, GM2, or galactocerebroside. Furthermore, the neoglycoprotein containing the terminal alpha2-6-linked sialic acid and the ganglioside GT1b inhibited JCV infection in the susceptible cell line IMR-32. These results suggest that the oligosaccharides of glycoproteins and glycolipids work as JCV receptors and may be feasible as anti-JCV agents.
Gangliosides↗
Nested PCR for detection of BK virus and JC virus DNA.
BACKGROUND: A nested polymerase chain reaction (PCR) was developed to detect BK virus (BKV) and JC virus (JCV) DNA sequences. The unique clevage site for BamHI restriction enzyme was located in the JCV amplimer and cleavage was used to differentiate between BKV and JCV. STUDY DESIGN: Twenty-three urine specimens from 17 bone marrow recipients with haemorrhagic cystitis and one liver transplant patient were tested for the presence of BKV and JCV DNA. Four brain tissue specimens (paraffin embedded brain tissues and a fresh frozen brain biopsy) and 5 cerebrospinal fluids from 3 AIDS patients and one liver transplant patient, all with progressive multifocal leukoencephalopathy (PML), were also examined by PCR. RESULTS: The sensitivity of the PCR was 10 genomes for each virus. BKV DNA was detected in 15 urine specimens from 12 bone marrow transplant patients. JCV DNA was detected in 4 cerebrospinal fluids and 4 brain tissues from patients with PML. CONCLUSION: Our results show that the nested PCR is a sensitive and rapid assay that can be used for diagnosis of BKV and JCV infections. The cerebrospinal fluid appears to be a suitable material for diagnosis of JC virus reactivation in the brain.
Journal Article↗
Detection of BK virus and JC virus DNA in urine samples from immunocompromised (HIV-infected) and immunocompetent (HIV-non-infected) patients using polymerase chain reaction and microplate hybridisation.
BACKGROUND: The majority of the human population is infected with two human polyomaviruses BK virus (BKV) and JC virus (JCV) during childhood. After initial infection both viruses persist within renal system. Reactivation of both viruses may be linked with immunodeficiency or immunosuppressive therapy. OBJECTIVE: To evaluate the relationship between immunodeficiency and viruria, prevalence of BK and JC viruria over time was investigated in a cohort of HIV seropositive individuals at different stages of disease. The excretion in this group was compared with virus excretion in their HIV seronegative partners and in an unselected cohort of patients attending a Genito-Urinary Medicine (GUM) clinic. STUDY DESIGN: The excretion of BKV and JCV DNA in multiple urine samples from HIV-infected patients at different stages of disease and their HIV-negative partners, and in single samples from a cohort of patients at a GUM clinic was investigated. A microplate hybridisation method was developed to increase both the sensitivity and specificity of detection of the PCR product. The method was also applied to estimate the DNA copy numbers of BKV and JCV in urine samples. RESULTS: Within the HIV group, the level of immunosuppression (CD4+ category) was not associated with JCV viruria. By contrast, there was a modest correlation between immunodeficiency as indicated by a decline in CD4+ count and BKV viruria. Shedding of both BKV and JCV DNA together in urine samples of HIV-infected patients was much higher than in control groups (P = 0.02), indicating that HIV infection may associate with polyomavirus reactivation. The incidence of flu-like syndrome was much higher in HIV-infected asymptomatic individuals than acquired immunodeficiency syndrome (AIDS)-related complex (ARC)/AIDS patients. In general, the concentration of BKV DNA viruria (DNA copy number) was dependent to CD4+ counts (P = 0.008) while concentration of JCV DNA was independent to CD4+ cell count (P = 0.54). The prevalence of BKV and JCV DNA in patients who were infected with C. trachomatis was 9/50 (18%) and 11/50 (22%), respectively. BKV and JCV DNA was detected in 3/19 (15%) and 2/19 (10%) of patients who were infected with N. gonorrhoea. Results suggested that persons infected with C. trachomatis were more likely to show BKV and JCV viruria. CONCLUSION: These results confirm that shedding of BK and JC viruses in urine is not exclusively found in immunosupression, it may also occur in healthy individuals. The frequency of virus excretion is however, apparently increased in HIV-infected patients, although no firm statistical difference could be established. One of the interesting aspects of these findings was the relatively high incidence of BKV and JCV viruria in both control groups, i.e. HIV-negative partners of HIV-infected patients and patients attending a GUM clinic.
Adolescent↗
A serological investigation of BK virus and JC virus infections in recipients of renal allografts.
BK virus (BKV) and JC virus (JCV) infections were evaluated in a serological study of 496 renal transplant recipients and their donors. A seropositive donor increased the rate of primary and reactivation infections with BKV and of primary infections with JCV. BKV infection rates were not influenced by the source of the renal allograft (cadaver versus living related donor); however, primary JCV infections occurred more often in recipients of seropositive cadaveric kidneys. Reactivated JCV infections occurred less frequently in patients treated with antilymphocyte preparation. BKV and JCV infections in renal transplant recipients may be caused either by reactivation of the recipient's latent virus or by virus from the donor kidney. These infections are, however, not associated with adverse outcome (death, high serum creatinine level, or loss of renal function) in the recipient in the early post-transplant period.
Antibodies, Viral↗
Serological cross-reactivities between antibodies to simian virus 40, BK virus, and JC virus assessed by virus-like-particle-based enzyme immunoassays.
Enzyme immunoassays (EIAs) for detection of serum antibodies to simian virus 40 (SV40), BK virus (BKV), and JC virus (JCV) were developed by using virus-like-particles (VLPs) produced in insect cells from recombinant baculoviruses expressing the VP1 protein of the respective virus. Rhesus macaque sera with neutralizing antibodies to SV40 showed a high level of reactivity in the SV40 VLP-based EIA, and these sera also showed lower levels of reactivity in the BKV and JCV VLP-based EIAs. Rhesus macaque sera negative for neutralizing antibodies to SV40 were negative in all three EIAs. Competitive binding assays showed that SV40 VLPs inhibited BKV reactivity. In rhesus macaque sera, high optical density (OD) values for antibodies to SV40 VLPs were correlated with high OD values for antibodies to BKV but not with high OD values for antibodies to JCV VLPs. Human sera with neutralizing antibodies to SV40 were more reactive to SV40 VLPs than human sera without neutralizing antibodies to SV40. The greater SV40 reactivities of human sera were correlated with greater reactivities to BKV VLPs but not JCV VLPs. These data suggest that cross-reactivity with BKV antibodies may account for part of the low-level SV40 reactivity seen in human sera. With their greater versatility and their suitability for large-scale testing, the VLP-based EIAs for SV40, BKV, and JCV are likely to contribute to a better understanding of the biology of these viruses.
Animals↗
Incidence of BK virus and JC virus viruria in human immunodeficiency virus-infected and -uninfected subjects.
BK virus (BKV) and JC virus (JCV) are present within the renal system of most adults. Reactivation may be linked to immunodeficiency, since many of the extant virus strains have been isolated from urine or kidney tissue of patients who were receiving immunosuppressive therapy or who had disorders of the immune system. To more critically evaluate the relationship between immunodeficiency and viruria, urine samples from individuals infected with human immunodeficiency virus (HIV) with various degrees of immunodeficiency were screened for the presence of viral DNA. JCV viruria occurred in 24%-27% of immunocompetent control subjects and was not increased with immunodeficiency. By contrast, there were both qualitative and quantitative changes in BKV viruria in immunodeficient subjects. The incidence of BKV viruria was increased, and some immunodeficient subjects shed BKV at levels up to 3000 times greater than levels shed by any of the nonimmunodeficient controls. DNA sequence rearrangements in the viral regulatory region did not appear to be required for shedding of virus, although they were present in approximately 20% of samples.
BK Virus↗
Prevalence of BK virus and JC virus in peripheral blood leukocytes and normal arterial walls in healthy individuals in China.
Several studies have demonstrated that BK virus (BKV) and JC virus (JCV) establish latent infection in peripheral blood leukocytes (PBLs) of healthy individuals; however, the main populations studied are European. In this study, the prevalence of BKV and JCV DNA in PBLs from healthy adult individuals and umbilical cord blood from newborn children in China was detected by semi-nested polymerase chain reaction (snPCR) followed by restriction enzyme analysis. The results suggest that the healthy adult Chinese population harbors BKV and JCV DNA in peripheral leukocytes. Overall, the prevalence of BKV and JCV DNA in PBLs of healthy adult individuals was 42.1% and 7.8%, respectively. The overall prevalence of BKV DNA was significantly higher than that of JCV DNA. None of the umbilical cord blood samples from newborn children were positive for BKV and JCV DNA. To understand further the target tissues involved in establishment of BKV and JCV latency in healthy individuals, the presence of DNA from both viruses was detected in normal arterial wall samples from 20 young trauma victims by the same method used for leukocyte DNA. BKV DNA was detected alone in 20% of samples tested; JCV DNA was not detected alone in any of the samples. DNA from both viruses was found in 5% of samples. This is the first report to show that normal arterial walls of healthy individuals may be another target site of latency for BKV and JCV.
Adolescent↗
Persistence of DNA sequences of BK virus and JC virus in normal human tissues and in diseased tissues.
Available evidence suggests that BK virus (BKV) and JC virus (JCV) persist in the kidneys of healthy individuals after primary infection and may reactivate when the host's immune response is impaired. Data supporting this hypothesis are presented. A previous study had shown BKV to be present in the kidneys of eight (57%) of 14 subjects. In the present study, which extended the investigation to a total of 30 subjects, BKV DNA was found in the renal tissues of 10 (33%) subjects, and JCV DNA was found in the renal tissues of three (10%) subjects. The viral DNA detected appeared not to be integrated with host DNA and to be isolated in foci. Investigation of normal and diseased brain tissue, including tissue from six subjects with multiple sclerosis, failed to reveal the presence of either JCV DNA or BKV DNA.
Adolescent↗
Investigation of human urine for genomic sequences of the primate polyomaviruses simian virus 40, BK virus, and JC virus.
Recent reports of the detection of simian virus 40 (SV40) nucleotide sequences in ependymomas, choroid plexus tumors, osteosarcomas, and mesotheliomas have raised the possibility that SV40, which naturally infects Asian macaques, is circulating among humans. This possibility was examined by performing polymerase chain reaction assays on urine samples of 166 homosexual men, 88 of them human immunodeficiency virus (HIV)-seropositive, for genomic sequences of SV40 as well as of human polyomaviruses BK virus (BKV) and JC virus (JCV). Tests with masked urine specimens spiked with SV40-transformed cells were included to monitor the SV40 assay. SV40, BKV, and JCV sequences were identified, respectively, in 0, 14%, and 34% of the urine specimens. JCV viruria was far more common (37%) than BKV viruria (5%) in HIV-seronegative persons. HIV infection and more severe immunosuppression were associated with a higher frequency of BKV viruria. In summary, SV40 viruria was not detected among homosexual men who shed human polyomaviruses at a high frequency.
AIDS-Related Opportunistic Infections↗
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 DNAs were 10 and 100 copies, respectively. Hybridization with the oligonucleotide probes was specific for each virus. A total of 57 urine samples from three groups of subjects were processed by DNA extraction or boiling and were tested by PCR. Urine samples collected from immunosuppressed patients (n = 11) and previously documented to be positive for BKV, JCV, or both were positive by PCR. Ten percent of urine samples from healthy adults (n = 30) that were previously negative for BKV and JCV were positive for one or both viruses by PCR. Urine samples (n = 16) from four seronegative bone marrow transplant recipients were uniformly negative for BKV. JCV was detected in deparaffinized brain tissue from a patient with progressive multifocal leukoencephalopathy. Specific diagnosis of virus in clinical specimens could be made within 1 day of receipt of the specimens. The PCR method is attractive for use in diagnosing polyomavirus infections because of its sensitivity, specificity, and rapid turnaround time.
BK Virus↗
Detection of Toxoplasma gondii, Epstein-Barr virus, and JC virus DNAs in the cerebrospinal fluid in acquired immunodeficiency syndrome patients with focal central nervous system complications.
OBJECT: Toxoplasmic encephalitis (TE), primary central nervous system lymphoma (PCNSL) and progressive multifocal leukoencephalopathy (PML) are major central nervous system (CNS) diseases in patients with acquired immunodeficiency syndrome (AIDS). We assessed the diagnostic value of polymerase chain reaction (PCR) in the detection of DNAs of Toxoplasma gondii (T. gondii), Epstein-Barr virus (EBV) and JC virus (JCV) in the cerebrospinal fluid (CSF). METHODS: We compared the PCR results with those of pathological findings at autopsy. PATIENTS OR MATERIALS: The present study included 23 autopsies representing those in whom CSF samples were obtained before death while the patient was hospitalized or at autopsy. RESULTS: The threshold levels for PCR detection were 4 tachyzoites of T. gondii, 5-15 genomes of EBV and 10 genomes of JCV. We identified T. gondii DNA in 4 out of 5 autopsy-defined cases of TE, EBV DNA in 5 out of 5 cases with PCNSL, and JCV DNA in 2 out of 2 cases with PML. The specificity of PCR was 100% in TE, 78% in PCNSL, and 100% in PML. CONCLUSION: Although the number of cases was relatively small in this study, PCR correctly identified T. gondii DNA in those cases in which PML or PCNSL was the sole clinical diagnosis. Our results indicate that PCR examination of CSF is a clinically useful tool for the diagnosis of focal brain lesions in patients with AIDS.
Acquired Immunodeficiency Syndrome↗
Brain tumors of owl monkeys inoculated with JC virus contain the JC virus genome.
The DNA from astrocytomas that developed in adult owl monkeys 16 to 36 months after intracranial inoculation with JC virus (JCV) was examined for the presence of the JCV genome by hybridization to cloned JCV DNA. The JCV genome was found to be integrated into the cellular DNA in all tumors examined. There was no JCV DNA in normal, uninvolved brain tissue from the same animals. Integration of the genome occurred at a limited number of sites in the cellular DNAs, indicating a clonal origin for the tumors, but none of the tumors had integration sites in common. In all but one of the tumors, there was tandem, head-to-tail integration of two or more copies of the JC genome. In a tumor which had only one integration site and could be analyzed more extensively, there appeared to be a complete copy of the JCV genome present, although deletions of small portions of the genome would not have been detected.
Animals↗