title: Opportunistic DNA Recombination With Epstein-Barr Virus at Sites of Control Region Rearrangements Mediating JC Virus Neurovirulence.
abstract: We document a unique DNA recombination between polyomavirus JC (JC virus [JCV]) and Epstein-Barr virus (EBV) at sequences of JCV found infecting the brain. Archetype JCV is present in bone marrow and uroepithelial cells of most adults. During immunosuppression, JCV can infect the brain, causing a demyelinating disease, progressive multifocal leukoencephalopathy. Rearrangements in the archetype noncoding control region are necessary for neurovirulence. Two NCCR deletions and a duplication occur at sequences of homology with EBV, present latently in B cells, which may be coinfected with both viruses. Recombination between JCV and EBV occurs in B lymphoblasts at a sequence essential for JCV neurovirulence and in cerebrospinal fluid of immunosuppressed patients with multiple sclerosis, those susceptible to progressive multifocal leukoencephalopathy. Interviral recombination is a model for conferring advantages on JCV in the brain. It can alter a critical noncoding control region sequence and potentially facilitate use of EBV DNA abilities to transfer among different cell types.
authors.affiliation: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk.
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Wortman
authors.affiliation: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk.
authors.forename: Patric S
authors.initials: PS
authors.lastname: Lundberg
authors.affiliation: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk.
authors.forename: Ayuna V
authors.initials: AV
authors.lastname: Dagdanova
authors.affiliation: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk.
authors.forename: Pranav
authors.initials: P
authors.lastname: Venkataraman
authors.affiliation: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk.
authors.forename: Dianne C
authors.initials: DC
authors.lastname: Daniel
authors.affiliation: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Johnson
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D016867:Immunocompromised Host; D007577:JC Virus / Q000235:genetics* / Q000472:pathogenicity; D007968:Leukoencephalopathy, Progressive Multifocal / Q000821:virology*; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000821:virology; D011995:Recombination, Genetic / Q000235:genetics*
keywords: AIDS; DNA replication; PML; interviral recombination; multiple sclerosis; progressive multifocal leukoencephalopathy