title: JC virus load in cerebrospinal fluid and transcriptional control region rearrangements may predict the clinical course of progressive multifocal leukoencephalopathy.
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.
authors.affiliation: Fondazione Ettore Sansavini, Health Science Foundation, Lugo, Ravenna, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Delbue
authors.forename: Francesca
authors.initials: F
authors.lastname: Elia
authors.forename: Camilla
authors.initials: C
authors.lastname: Carloni
authors.forename: Eleonora
authors.initials: E
authors.lastname: Tavazzi
authors.forename: Enrico
authors.initials: E
authors.lastname: Marchioni
authors.forename: Silvia
authors.initials: S
authors.lastname: Carluccio
authors.forename: Lucia
authors.initials: L
authors.lastname: Signorini
authors.forename: Stefano
authors.initials: S
authors.lastname: Novati
authors.forename: Renato
authors.initials: R
authors.lastname: Maserati
authors.forename: Pasquale
authors.initials: P
authors.lastname: Ferrante
mesh_terms: D000328:Adult; D002555:Cerebrospinal Fluid / Q000821:virology*; D004279:DNA, Viral / Q000134:cerebrospinal fluid / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000134:cerebrospinal fluid / Q000821:virology; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D007577:JC Virus / Q000235:genetics / Q000502:physiology*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000134:cerebrospinal fluid / Q000821:virology*; D008297:Male; D025542:Neurofibromin 1 / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D014158:Transcription, Genetic; D019562:Viral Load
chemical_list: D004279:DNA, Viral; D025542:Neurofibromin 1; D012367:RNA, Viral