title: Rearrangement of the JC virus regulatory region sequence in the bone marrow of a patient with rheumatoid arthritis and progressive multifocal leukoencephalopathy.
abstract: The polyomavirus JC (JCV) is the etiologic agent of progressive multifocal leukoencephalopathy (PML). JCV remains quiescent in kidneys, where it displays a stable archetypal regulatory region (RR). Conversely, rearranged JCV RR, including tandem repeat patterns found in the central nervous system (CNS) of PML patients, have been associated with neurovirulence. The precise site and mechanism of JCV RR transformation is unknown. We present herein a patient with rheumatoid arthritis treated with methotrexate, who developed PML and had a rapid fatal outcome. JCV DNA polymerase chain reaction (PCR) was positive in cerebrospinal fluid (CSF), bone marrow, blood, and urine. Double-immunohistochemical staining demonstrated that 9% of bone marrow CD138(+) plasma cells sustained productive infection by JCV, accounting for 94% of JCV-infected cells. JCV RR analysis revealed archetype and rearranged RR forms in bone marrow, whereas RR with tandem repeat was predominant in blood. These results suggest that the bone marrow may be a potential site of JCV pathogenic transformation. Further studies will be needed to determine the prevalence of JCV in bone marrow of immunosuppressed individuals at risk of PML and characterize the RR and phenotype of these JCV isolates.
authors.affiliation: Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Marzocchetti
authors.forename: Christian
authors.initials: C
authors.lastname: Wuthrich
authors.forename: Chen S
authors.initials: CS
authors.lastname: Tan
authors.forename: Troy
authors.initials: T
authors.lastname: Tompkins
authors.forename: Francisco
authors.initials: F
authors.lastname: Bernal-Cano
authors.forename: Parul
authors.initials: P
authors.lastname: Bhargava
authors.forename: Allan H
authors.initials: AH
authors.lastname: Ropper
authors.forename: Igor J
authors.initials: IJ
authors.lastname: Koralnik
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000235:genetics; D001853:Bone Marrow / Q000821:virology*; D001921:Brain / Q000821:virology; D002555:Cerebrospinal Fluid / Q000821:virology; D004279:DNA, Viral / Q000032:analysis / Q000097:blood / Q000134:cerebrospinal fluid* / Q000235:genetics; D015321:Gene Rearrangement; D006801:Humans; D007577:JC Virus / Q000235:genetics / Q000302:isolation & purification*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000235:genetics / Q000503:physiopathology* / Q000821:virology; D008279:Magnetic Resonance Imaging; D008297:Male; D008969:Molecular Sequence Data; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D020080:Tandem Repeat Sequences / Q000235:genetics
chemical_list: D004279:DNA, Viral