Survey for the presence of BK, JC, KI, WU and Merkel cell polyomaviruses in human brain tissues (original) (raw)
Related papers
Journal of Medical Virology, 1995
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system, which is thought to be a result of the reactivation of JC virus (JCV), a human polyomavirus. The disease occurs in individuals with immunosuppression and in recent years there has been an increase in PML cases due t o AIDS. A nested polymerase chain reaction (n-PCR) was employed to detect JCV and BK virus (BKV) DNA in brain tissue collected postmortem from 28 AIDS patients with PML and from 13 patients without PML, but with other diagnoses, including solid tumors, Alzheimer's disease, thromboembolism, myocardial infarction and acute cerebrovascular diseases. All 28 brain specimens from the patients with PML were positive for JCV DNA when tested by n-PCR and three of the latter were also positive for BKV DNA. These results were confirmed by an enzyme restriction analysis and a DNA hybridization assay. Interestingly, in this study, JCV DNA was also found in 6 brain tissue specimens from 4 subjects with diseases unrelated to PML or AIDS. All the brain specimens from the control group were negative for BKV DNA. The results confirm that the n-PCR is a useful tool for PML diagnosis. The presence of JCV DNA in the brain tissue of patients without PML is particularly important since it indicates that JCV could be latent in the brains of immunocompetent individuals. Moreover, detection of simultaneous presence of JCV and BKV in the brain tissue of the patients with PML demonstrates that BKV may also infect the human brain without causing any apparent neurological disease.
Brain Tumors and Polyomaviruses
Journal of Neurovirology, 2003
(SV40) have attracted much attention in the past decade due to their repeated isolation from various human tumors, including those originating from the central nervous system (CNS). JCV and BKV are considered to be ubiquitous human pathogens that become reactivated under impaired physiological conditions such as immunosuppression. Productive replication of JCV and BKV induces diseases such as progressive multifocal leukoencephalopathy in the brain and hemorrhagic or nonhemorrhagic cystitis and nephritis in the kidney. JCV DNA sequences have been isolated from a number of human CNS tumors, including medulloblastoma, ependymoma, and a broad range of glial-origin neoplasms. SV40, once believed to be a monkey virus, has now been isolated from a variety of human cancer cells, including mesothelioma, ependymoma, and non-Hodgkin's lymphoma. In this mini-review, the authors focused their attention on the possible involvement of polyomaviruses, such as JCV, BKV, and SV40, with human brain tumors. Journal of NeuroVirology (2003) 9, 173-182.
Journal of Virology, 1981
Human polyomavirus JC DNA was purified directly from the diseased brain tissue of two patients with progressive multifocal leukoencephalopathy (PML) by a method employing differential salt precipitation (B. Hirt, J. Mol. Biol. 26:365-369, 1967). Each of the viral genomes (JC-NIH-1 and JC-NIH-2) was molecularly cloned intact in Escherichia coli, using pBR322, at their unique EcoRI (0.00 map unit) and BamHI (0.51 map unit) sites. The JC-NIH-1 genome was approximately 50 base pairs larger and the JC-NIH-2 genome was approximately 50 base pairs smaller than the prototype human polyomavirus JC (Mad-1) DNA. Analysis of the restriction endonuclease cleavage fragments of these two DNAs and the human polyomavirus JC (Mad-1) DNA revealed only slight differences which mapped in a region of the genome extending from 0.67 to 0.74 map unit. From previous homology studies, this region of variance corresponds to the noncoding region to the late side of the origin of DNA replication.
Detection of reactivation and size variation in the regulatory region of JC virus in brain tissue
Journal of Clinical Pathology, 1993
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 ofJC and BK polyomaviruses, respectively. A third primer (JC3), internal to JCI and JC2, was designed to be specific for JC virus. The specificity ofJC3 was investigated by amplifying plasmids with BK or JC virus genomes. Sensitivity was estimated by 57 No known predisposing cause
Human Polyomavirus-Associated Cerebral Disorders in the Post-HAART Era
Pathology Research International, 2011
Human polyomavirus JC is the causative agent of a deadly form of sudden onset dementia, progressive multifocal leukocoencephalopathy (PML). PML is highly prevalent in immunodeficient populations, specially those undergoing chemotherapy, immunosuppressive treatments for autoimmune conditions, and HIV-1/AIDS patients. In fact, before the highly active antiretroviral therapy (HAART) regimens became available, PML was a leading cause of death in HIV-1 seropositive individuals. However, patients under HAART show increased survival times with better prognoses. In this report we described the main differences between PML before and after the HAART era; highlighting the new patterns of presentation, the neurotropism of other human polyomaviruses, and the increased prevalence of immune reconstitution inflammatory syndrome (IRIS), as a complication of PML in patients under HAART. Lastly, we propose a revised classification of human poliomavirus-associated cerebral disorders that may reflect m...
PLOS One, 2009
Background: BK and JC polyomaviruses (BKV and JCV) are potentially oncogenic and have in the past inconclusively been associated with tumours of the central nervous system (CNS), while BKV has been hinted, but not confirmed to be associated with neuroblastomas. Recently three new polyomaviruses (KIPyV, WUPyV and MCPyV) were identified in humans. So far KIPyV and WUPyV have not been associated to human diseases, while MCPyV was discovered in Merkel Cell carcinomas and may have neuroepithelial cell tropism. However, all three viruses can be potentially oncogenic and this compelled us to investigate for their presence in childhood CNS and neuroblastomas.
Advances in the Biology of JC Virus and Induction of Progressive Multifocal Leukoencephalopathy
Journal of Neurovirology, 2003
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. Journal of NeuroVirology (2003) 9, 236-246.
Journal of Medical Virology, 1993
JC virus (JCV) DNA was detected by polymerase chain reaction (PCR) amplification in the cerebrospinal fluid (CSF) of 10 of 13 patients with a diagnosis of progressive multifocal leukoencephalopathy (PML) previously confirmed by histological and virological techniques. It was not found in 42 CSF samples from 41 patients who did not have PML. Four sets of primers were used to amplify polyomavirus DNA. One was from the region of the genome coding the T antigen, a conserved region common to JC and BK viruses. A second set nested to these was used as a confirmatory test in a secondary PCR. The remaining two were from the region of the genome coding VPI, one specific for JCV and the other for BKV. CSF did not inhibit the PCR and preliminary DNA extraction was not considered necessary.
Detection of JC virus DNA fragments but not proteins in normal brain tissue
Annals of Neurology, 2008
ObjectiveProgressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease of the white matter affecting immunocompromised patients that results from the cytolytic destruction of glial cells by the human neurotropic JC virus (JCV). According to one model, during the course of immunosuppression, JCV departs from its latent state in the kidney and after entering the brain, productively infects and destroys oligodendrocytes. The goal of this study was to test the hypothesis that JCV may reside in a latent state in a specific region of the brains of immunocompetent (non-PML) individuals without any neurological conditions.Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease of the white matter affecting immunocompromised patients that results from the cytolytic destruction of glial cells by the human neurotropic JC virus (JCV). According to one model, during the course of immunosuppression, JCV departs from its latent state in the kidney and after entering the brain, productively infects and destroys oligodendrocytes. The goal of this study was to test the hypothesis that JCV may reside in a latent state in a specific region of the brains of immunocompetent (non-PML) individuals without any neurological conditions.MethodsGene amplification was performed together with immunohistochemistry to examine the presence of JCV DNA sequences and expression of its genome in five distinct regions of the brain from seven immunocompetent non-PML individuals.Gene amplification was performed together with immunohistochemistry to examine the presence of JCV DNA sequences and expression of its genome in five distinct regions of the brain from seven immunocompetent non-PML individuals.ResultsAlthough no viral proteins were expressed in any of these cases, fragments of the viral DNA were present in various regions of normal brain. Laser-capture microdissection showed the presence of JCV DNA in oligodendrocytes and astrocytes, but not in neurons.Although no viral proteins were expressed in any of these cases, fragments of the viral DNA were present in various regions of normal brain. Laser-capture microdissection showed the presence of JCV DNA in oligodendrocytes and astrocytes, but not in neurons.InterpretationThe detection of fragments of viral DNA in non-PML brain suggests that JCV has full access to all regions of the brain in immunocompetent individuals. Thus, should the immune system become impaired, the passing and/or the resident virus may gain the opportunity to express its genome and initiate its lytic cycle in oligodendrocytes. The brain as a site of JCV latency is a possibility. Ann Neurol 2008; 64:379–387The detection of fragments of viral DNA in non-PML brain suggests that JCV has full access to all regions of the brain in immunocompetent individuals. Thus, should the immune system become impaired, the passing and/or the resident virus may gain the opportunity to express its genome and initiate its lytic cycle in oligodendrocytes. The brain as a site of JCV latency is a possibility. Ann Neurol 2008; 64:379–387