AMPLIFICATION OF JC VIRUS REGULATORY DNA-SEQUENCES FROM CEREBROSPINAL-FLUID - DIAGNOSTIC-VALUE FOR PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY

Citation
C. Sugimoto et al., AMPLIFICATION OF JC VIRUS REGULATORY DNA-SEQUENCES FROM CEREBROSPINAL-FLUID - DIAGNOSTIC-VALUE FOR PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY, Archives of virology, 143(2), 1998, pp. 249-262
Citations number
38
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Virology
Journal title
ISSN journal
0304-8608
Volume
143
Issue
2
Year of publication
1998
Pages
249 - 262
Database
ISI
SICI code
0304-8608(1998)143:2<249:AOJVRD>2.0.ZU;2-W
Abstract
Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinat ing disease in the central nervous system caused by a ubiquitous human polyomavirus designated as JC virus (JCV). PML affects individuals wi th decreased immune competence and is now one of the common opportunis tic infections in patients with AIDS. JCV DNAs in the brain of PML pat ients contain various PML-type regulatory regions that were generated from the archetypal regulatory region during persistence. Recently, ma ny studies have suggested that detection of JCV DNA from the cerebrosp inal fluid (CSF) may offer a tool for diagnosing PML. However, in all of these studies, coding Sequences within the T antigen or capsid prot ein gene have been targeted for amplification. To amplify the JCV regu latory region, we established a nested PCR that could efficiently ampl ify the regulatory region from most JCV subtypes prevalent in the worl d. Using this PCR, we amplified JCV regulatory regions from the CSF sa mples from 4 patients strongly suspected of PML, whereas amplification was negative from 80 CSF samples from patients without PML. Sequencin g of the amplified fragments PML patients, we analyzed the structures of regulatory regions derived from the brain as well as CSF. In each o f these cases, the major regulatory sequence of both origins were iden tical. This finding indicates that JCV DNA in brain lesions is excrete d in the CSF. Since the structures of PML-type JCV regulatory regions are unique to individual patients, the current PCR, if the amplified f ragments are sequenced, can eliminate false positives that may arise f rom contaminations.