JC virus load in cerebrospinal fluid and transcriptional control region rearrangements may predict the clinical course of progressive multifocal leukoencephalopathy
Articolo
Data di Pubblicazione:
2012
Citazione:
JC virus load in cerebrospinal fluid and transcriptional control region rearrangements may predict the clinical course of progressive multifocal leukoencephalopathy / S. Delbue, F. Elia, C. Carloni, E. Tavazzi, E. Marchioni, S. Carluccio, L. Signorini, S. Novati, R. Maserati, P. Ferrante. - In: JOURNAL OF CELLULAR PHYSIOLOGY. - ISSN 0021-9541. - 227:10(2012), pp. 3511-3517.
Abstract:
Progressive multifocal leukoencephalopathy (PML) is a severe disease of the central nervous system (CNS), caused by infection with the Polyomavirus JC virus (JCV). Because there are no known treatments or prognostic factors, we performed a long-term study focusing mainly on cerebrospinal fluid (CSF) samples from PML patients to describe the virological features akin to the different forms of the disease. Twenty-eight PML patients were enrolled: 10 HIV-1+ patients with classical PML (CPML), 9 HIV-1+ patients with slowly progressing or stable neurological symptoms (benign PML), 3 HIV-1+ asymptomatic patients, and 6 HIV-1-negative patients. CSF, urine, and blood samples were collected at the enrollment (baseline) and every 6 months afterwards when possible. The JCV DNA and HIV-1 RNA loads were determined, and the JCV strains were characterized. At baseline, the mean CSF JCV load was log 6.0 ± 1.2 copies/ml for CPML patients, log 4.0 ± 1.0 copies/ml for benign PML patients, log 4.2 ± 0.5 copies/ml for asymptomatic PML patients, and log 5.8 ± 1.3 copies/ml for HIV-1-negative PML patients (CPML vs. benign: P < 0.01; CPML vs. asymptomatic: P < 0.05; HIV-1 negative vs. benign: P < 0.01). Organization of the JCV transcriptional control region (TCR) showed unusual archetype structures in two long-term survival patients; the NF1 sequence was found most commonly, whereas the Sp1 binding site was the most common for both CPML patients and HIV-1 negative patients. Our results suggest that the JCV load in the CSF and the organization of the TCR should be considered as indicators of PML clinical outcome.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
active antiretroviral therapy; human-immunodeficiency-virus; increased frequency; polyomavirus; replication; sequences; promoter; urine; brain; expression
Elenco autori:
S. Delbue, F. Elia, C. Carloni, E. Tavazzi, E. Marchioni, S. Carluccio, L. Signorini, S. Novati, R. Maserati, P. Ferrante
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