title: BK virus regulatory region rearrangements in brain and cerebrospinal fluid from a leukemia patient with tubulointerstitial nephritis and meningoencephalitis.
abstract: BK virus (BKV) was recovered by polymerase chain reaction (PCR) from brain, kidney, lung, urine, and cerebrospinal fluid (CSF) of a fatal case of BKV tubulointerstitial nephritis with dissemination to lung and brain. Viral regulatory regions in PCR-amplified urine and the lung samples were identical to the archetypal structure, WWT. In the brain and CSF, a rearranged sequence predominated, however. A 94-bp deletion preceded a 71-bp tandem duplication because the same 94-bp segment was deleted from both copies. PCR-amplified regulatory region products were cloned and sequenced to define further the extent of the rearranged structures. Two kidney clones were archetypal, whereas two others were rearranged differently from the brain and from each other. In contrast to the brain clones, the kidney rearrangements seemed to involve deletion after duplication. Three of four brain clones sequenced were identical to the rearrangement found to dominate in the PCR product. A fourth clone showed two short deletions without any duplication. The four CSF clones all showed rearrangements identical to that which was amplified by PCR from CSF and brain. This represents the first molecular analysis of a BKV strain obtained from a central nervous system infection, and it reveals regulatory region rearrangements reminiscent of those described in JC virus from brains with progressive multifocal leukoencephalopathy. We suggest that the presence in the CSF of BKV with a dominant rearranged regulatory region may be useful in the diagnosis of BKV meningoencephalitis secondary to BKV nephritis.
authors.affiliation: Neurotoxicology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-4126, USA. stonerg@ninds.nih.gov
authors.forename: Gerald L
authors.initials: GL
authors.lastname: Stoner
authors.forename: Raj
authors.initials: R
authors.lastname: Alappan
authors.forename: David V
authors.initials: DV
authors.lastname: Jobes
authors.forename: Caroline F
authors.initials: CF
authors.lastname: Ryschkewitsch
authors.forename: Marie L
authors.initials: ML
authors.lastname: Landry
mesh_terms: D001739:BK Virus / Q000235:genetics* / Q000302:isolation & purification; D001483:Base Sequence; D001921:Brain / Q000821:virology*; D003001:Cloning, Molecular; D015321:Gene Rearrangement / Q000235:genetics*; D006801:Humans; D007668:Kidney / Q000821:virology; D007938:Leukemia / Q000134:cerebrospinal fluid / Q000235:genetics / Q000821:virology*; D008168:Lung / Q000821:virology; D008297:Male; D008590:Meningoencephalitis / Q000134:cerebrospinal fluid / Q000235:genetics / Q000821:virology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009395:Nephritis, Interstitial / Q000134:cerebrospinal fluid / Q000235:genetics / Q000821:virology*; D027601:Polyomavirus Infections / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D014412:Tumor Virus Infections / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000235:genetics; D014556:Urine / Q000821:virology