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.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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DNA-Binding Proteins / biosynthesis
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Gene Expression*
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Genetic Association Studies
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Humans
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JC Virus / genetics*
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Leukoencephalopathy, Progressive Multifocal / genetics*
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Lymphocytes / immunology*
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Molecular Sequence Data
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Regulatory Sequences, Nucleic Acid*
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Risk Assessment
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Sequence Analysis, DNA
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Transcription Factors / biosynthesis
Substances
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DNA-Binding Proteins
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Transcription Factors
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SPIB protein, human
Associated data
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GENBANK/KF788287
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GENBANK/KF788288
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GENBANK/KF788289
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GENBANK/KF788290
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GENBANK/KJ001213
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GENBANK/KJ001214
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GENBANK/KJ001215
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GENBANK/KJ001216
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GENBANK/KJ001217
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GENBANK/KJ001218
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GENBANK/KJ001219
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GENBANK/KJ001220
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GENBANK/KJ001221
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GENBANK/KJ001222
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GENBANK/KJ001223