title: JC virus regulatory region rearrangements in the brain of a long surviving patient with progressive multifocal leukoencephalopathy.
abstract: JC virus (JCV) infection of oligodendrocytes causes demyelination in brains of patients with with progressive multifocal leukoencephalopathy (PML). Expansion of demyelination throughout the brain is not fully understood. The opportunity was taken to investigate the postmortem brain of a long surviving patient with PML for whom diagnosis was made 4 years before death based on pathological and virological findings of a brain biopsy. Four distinct regulatory sequences in the JCV genome were detected (designated as JW-1 to 4) from various regions of the necropsied brain. All regulatory sequences were rearranged forms that could be produced from the archetype by deletions and duplications. JW-1 and 2 shared some structural features not present in JW-3 and 4 and vice versa. JW-1 was distributed throughout the brain, whereas JW-2, 3, and 4 were restricted to only part of the brain. JW-1 and 2 had been detected in the initial brain biopsy 4 years earlier. These findings suggested that brain lesions in advanced stages were generated not only by expansion of the original variant (JW-1) of JCV but also by delayed growth of two other variants (JW-3 and 4).
authors.affiliation: Laboratory of Viral Infection, Division of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yogo
authors.forename: T
authors.initials: T
authors.lastname: Matsushima-Ohno
authors.forename: T
authors.initials: T
authors.lastname: Hayashi
authors.forename: C
authors.initials: C
authors.lastname: Sugimoto
authors.forename: M
authors.initials: M
authors.lastname: Sakurai
authors.forename: I
authors.initials: I
authors.lastname: Kanazawa
mesh_terms: D000328:Adult; D001344:Autopsy; D001483:Base Sequence / Q000235:genetics; D001706:Biopsy; D004279:DNA, Viral / Q000235:genetics*; D017809:Fatal Outcome; D020440:Gene Duplication; D015321:Gene Rearrangement / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D007577:JC Virus / Q000145:classification / Q000235:genetics* / Q000254:growth & development; D007968:Leukoencephalopathy, Progressive Multifocal / Q000473:pathology* / Q000821:virology*; D008297:Male; D016133:Polymerase Chain Reaction; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D016415:Sequence Alignment; D017384:Sequence Deletion / Q000235:genetics
chemical_list: D004279:DNA, Viral