title: Lymphocyte gene expression and JC virus noncoding control region sequences are linked with the risk of progressive multifocal leukoencephalopathy.
abstract: Progressive multifocal leukoencephalopathy (PML)-derived noncoding control region (NCCR) sequences permitted greater early viral gene expression than kidney-associated NCCR sequences. This was driven in part by binding of the transcription factor Spi-B to unique PML-associated Spi-B binding sites. Spi-B is upregulated in developing B cells in response to natalizumab therapy, a known risk factor for PML. Naturally occurring JCV sequence variation, together with drug treatment-induced cellular changes, may synergize to create an environment leading to an increased risk of PML.
authors.affiliation: Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Marshall
authors.forename: Michael W
authors.initials: MW
authors.lastname: Ferenczy
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Daley
authors.forename: Peter N
authors.initials: PN
authors.lastname: Jensen
authors.forename: Caroline F
authors.initials: CF
authors.lastname: Ryschkewitsch
authors.forename: Eugene O
authors.initials: EO
authors.lastname: Major
mesh_terms: D004268:DNA-Binding Proteins / Q000096:biosynthesis; D015870:Gene Expression; D056726:Genetic Association Studies; D006801:Humans; D007577:JC Virus / Q000235:genetics*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000235:genetics*; D008214:Lymphocytes / Q000276:immunology*; D008969:Molecular Sequence Data; D012045:Regulatory Sequences, Nucleic Acid; D018570:Risk Assessment; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000096:biosynthesis
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors; C076877:SPIB protein, human