Prognostic Significance of JC Virus DNA Levels in Cerebrospinal Fluid of Patients with HIV-Associated Progressive Multifocal Leukoencephalopathy

Bossolasco, Simona; Calori, Giliola; Moretti, Francesca; Boschini, Antonio; Bertelli, Davide; Mena, Maurizio; Gerevini, Simonetta; Bestetti, Arabella; Pedale, Rosa; Sala, Serena; Sala, Stefania; Lazzarin, Adriano; Cinque, Paola

doi:10.1086/427698

Cited by 139 publications

(85 citation statements)

References 28 publications

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“…In the first part of the present study, the levels of sensitivity of the new JC/BK Consensus PCR test appeared to be equivalent to those previously obtained by classical or real-time PCR assays for the detection of polyomavirus genomes (3,6,27). Evaluation of the specificity demonstrated the capacity of this new assay to perform the specific differential detection of JC or BK virus genomes whatever the levels of human polyomavirus DNA templates per reaction tube were (Table 1).…”

Section: Discussionsupporting

confidence: 76%

“…Several recent studies have demonstrated that real-time PCR technology could overcome many of these limitations and could be reliable tools for the rapid diagnosis of polyomavirus-related diseases in clinical practice. However, this PCR technology requires costly real-time PCR instrumentation and the development and the validation of specific fluorophore-labeled hybridization probes that allow the identifica-tion of human polyomaviruses in clinical samples (6,11,18,26,27).…”

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confidence: 99%

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New Commercially Available PCR and Microplate Hybridization Assay for Detection and Differentiation of Human Polyomaviruses JC and BK in Cerebrospinal Fluid, Serum, and Urine Samples

Moret¹,

Brodard²,

Barranger³

et al. 2006

J Clin Microbiol

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JC and BK human polyomaviruses (family Polyomaviridae) may cause severe neurological or urinary tract pathologies in immunocompromised hosts. In the present study, we evaluated a new commercially available PCR and microplate colorimetric hybridization assay for the standardized differential detection of JC virus (JCV) and BK virus (BKV) genomes in clinical samples. This JC/BK Consensus test was first evaluated by testing serial dilutions of JCV or BKV plasmid DNA standards and was then compared with an in-house reference PCR assay for the detection of JC and BK virus genomes in 70 cerebrospinal fluid (CSF) samples of patients with neurological disorders and in 75 serum or plasma samples and 125 urine samples of renal graft recipients. This new test allowed a limit of detection of 10 copies and 1 copy of JC and BK virus genomes, respectively, and was able to differentiate various levels of JCV, BKV, and mixed JCV and BKV DNA genomes in a single reaction tube. Our results showed 100% specificity and sensitivity for the JC/BK Consensus test with CSF samples. With serum or plasma samples, this test had a sensitivity and a specificity of 100% for both JCV and mixed JCV and BKV DNA detection and a sensitivity and a specificity of 100 and 97.8% for BKV DNA detection, respectively. With urine samples, the sensitivity and specificity were 100 and 96.6%, respectively, for JCV DNA detection; 100 and 89.4%, respectively, for BKV DNA detection; and 44.4 and 100%, respectively, for mixed JCV and BKV DNA detection. In conclusion, our data indicate that this new test, the JC/BK Consensus test, is valuable for the sensitive and specific differential detection of single JCV and BKV infections in CSF, serum or plasma, and urine samples. The use of this reliable PCR assay would improve the routine virological diagnosis as well as the clinical care of immunocompromised patients with polyomavirus-related pathologies.Human polyomaviruses JC and BK (family Polyomaviridae) are very similar viruses, based on their structures, DNA genome organizations, and nucleotide sequences. Both JC virus (JCV) and BK virus (BKV) share approximately 75% nucleotide homology with each other and 70% nucleotide homology with the simian polyomavirus simian virus 40 (21, 31). Human polyomaviruses JC and BK are endemic and infect a large proportion of healthy individuals worldwide (13,29). Primary infections with these viruses usually occur during childhood, are largely asymptomatic, and may result in transient viruria (7). Following primary infections, JCV and BKV both establish latent infections in renal tissues and can also be detected in the B lymphocytes of healthy adults (1, 9, 19). Polyomavirus-related diseases usually develop under conditions of severe cellular immunosuppression, such as organ transplantation, AIDS, and leukemia (20). JCV is the causative agent of progressive multifocal leukoencephalopathy (PML), which primarily occurs in AIDS patients (4,16,30), and it has been also identified as a causal agent of hemorrhagic cystitis and graft nephr...

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Section: Discussionsupporting

confidence: 76%

mentioning

confidence: 99%

New Commercially Available PCR and Microplate Hybridization Assay for Detection and Differentiation of Human Polyomaviruses JC and BK in Cerebrospinal Fluid, Serum, and Urine Samples

Moret¹,

Brodard²,

Barranger³

et al. 2006

J Clin Microbiol

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“…Due to the lack of effective antiviral therapy (13), the treatment of PML is based on improving overall immune functions. While this is difficult to achieve in cancer, chemotherapy, and transplantation, prompt antiretroviral therapy in HIV/AIDS patients has significantly improved PML survival, with increasing JCV-specific immune responses and declining intracerebral JCV replication (7,15,23,35,37). In patients diagnosed with PML after treatment with natalizumab for multiple sclerosis or inflammatory bowel disease, the removal of the monoclonal antibody by plasmapheresis has been tried to restore lymphocyte homing to, and the immune surveillance of, JCV replication sites in the central nervous system (38,40,52).…”

mentioning

confidence: 99%

Rearranged JC Virus Noncoding Control Regions Found in Progressive Multifocal Leukoencephalopathy Patient Samples Increase Virus Early Gene Expression and Replication Rate

Gosert

Kardas

Major

et al. 2010

J Virol

117

145

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Polyomavirus JC (JCV) infects ϳ60% of the general population, followed by asymptomatic urinary shedding in ϳ20%. In patients with pronounced immunodeficiency, including HIV/AIDS, JCV can cause progressive multifocal leukoencephalopathy (PML), a devastating brain disease of high mortality. While JCV in the urine of healthy people has a linear noncoding control region called the archetype NCCR (at-NCCR), JCV in brain and cerebrospinal fluid (CSF) of PML patients bear rearranged NCCRs (rr-NCCRs). Although JCV NCCR rearrangements are deemed pathognomonic for PML, their role as a viral determinant is unclear. We sequenced JCV NCCRs found in CSF of eight HIV/AIDS patients newly diagnosed with PML and analyzed their effect on early and late gene expression using a bidirectional reporter vector recapitulating the circular polyomavirus early and late gene organization. The rr-NCCR sequences were highly diverse, but all increased viral early reporter gene expression in progenitor-derived astrocytes, glia-derived cells, and human kidney compared to the expression levels with the at-NCCR. The expression of simian virus 40 (SV40) large T antigen or HIV Tat expression in trans was associated with a strong increase of at-NCCR-controlled early gene expression, while rr-NCCRs were less responsive. The insertion of rr-NCCRs into the JCV genome backbone revealed higher viral replication rates for rr-NCCR compared to those of the at-NCCR JCV in human progenitor-derived astrocytes or glia cells, which was abrogated in SV40 large T-expressing COS-7 cells. We conclude that naturally occurring JCV rr-NCCR variants from PML patients confer increased early gene expression and higher replication rates compared to those of at-NCCR JCV and thereby increase cytopathology.

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“…A cerebrospinal fluid (CSF) examination was done and it was normal. However, PCR was positive for JC virus with a value of >3.64 log copies/ ml [7]. Computerised tomography (CT) scan demonstrated multiple areas of non-enhancing lesions in white matter.…”

Section: Case Reportmentioning

confidence: 99%

Progressive Multifocal Leukoencephalopathy Associated with Pulmonary Tuberculosis in an Immuno-Compromised Indian Patient

Singh¹

2013

J AIDS Clin Res

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Prognostic Significance of JC Virus DNA Levels in Cerebrospinal Fluid of Patients with HIV-Associated Progressive Multifocal Leukoencephalopathy

Abstract: Measurement of JCV DNA levels in CSF samples may be a useful virological marker for management of PML in patients receiving HAART.

Cited by 139 publications

References 28 publications

New Commercially Available PCR and Microplate Hybridization Assay for Detection and Differentiation of Human Polyomaviruses JC and BK in Cerebrospinal Fluid, Serum, and Urine Samples

New Commercially Available PCR and Microplate Hybridization Assay for Detection and Differentiation of Human Polyomaviruses JC and BK in Cerebrospinal Fluid, Serum, and Urine Samples

Rearranged JC Virus Noncoding Control Regions Found in Progressive Multifocal Leukoencephalopathy Patient Samples Increase Virus Early Gene Expression and Replication Rate

Progressive Multifocal Leukoencephalopathy Associated with Pulmonary Tuberculosis in an Immuno-Compromised Indian Patient

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