Brain and kidney of progressive multifocal leukoencephalopathy patients contain identical rearrangements of the JC virus promoter/enhancer.
The kidneys of six progressive multifocal leukoencephalopathy (PML) patients were examined by PCR amplification for the presence of JC virus. Amplification of three different areas of the viral genome from multiple samples of each kidney revealed three that were positive for the virus. The use of a PCR-based typing assay on all tissue samples, and cloned sequences from the viral coding region from each positive kidney showed that the same viral genome was present in the kidney as in the brain of the patient. Regulatory region clones all had the archetypal promoter/enhancer structure. However, when PCR fragments from the regulatory region were digested with a restriction enzyme which cuts in region D, the region most often deleted in PML-type promoters, a low level of undigested DNA remained. This DNA refractory to digestion had a rearranged sequence identical to that of the unique rearranged promoter in the brain of each patient.
Laboratory of Experimental Neuropathology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
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D001483:Base Sequence; D001921:Brain / Q000821:virology*; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics; D015321:Gene Rearrangement; D005838:Genotype; D006801:Humans; D007577:JC Virus / Q000235:genetics* / Q000302:isolation & purification; D007668:Kidney / Q000821:virology*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000821:virology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D017422:Sequence Analysis, DNA
D004279:DNA, Viral; C046184:endodeoxyribonuclease PaeI; D015252:Deoxyribonucleases, Type II Site-Specific