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.
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.
|Titolo:||JC virus load in cerebrospinal fluid and transcriptional control region rearrangements may predict the clinical course of progressive multifocal leukoencephalopathy|
DELBUE, SERENA (Primo)
FERRANTE, PASQUALE (Corresponding)
|Parole Chiave:||active antiretroviral therapy; human-immunodeficiency-virus; increased frequency; polyomavirus; replication; sequences; promoter; urine; brain; expression|
|Settore Scientifico Disciplinare:||Settore MED/07 - Microbiologia e Microbiologia Clinica|
|Data di pubblicazione:||2012|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1002/jcp.24051|
|Appare nelle tipologie:||01 - Articolo su periodico|
File in questo prodotto:
|Delbue_et_al-2012-Journal_of_Cellular_Physiology.pdf||Publisher's version/PDF||Administrator Richiedi una copia|