title: Alterations of DNA damage repair pathways resulting from JCV infection.
abstract: Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disorder of the CNS caused by infection of glial cells with the polyomavirus, JCV. Here we report that genomic stability and DNA repair are significantly dysregulated by JCV infection of human astrocytes. Metaphase spreads exhibited increased ploidy correlating with duration of infection. Increased micronuclei formation and phospho-Histone2AX expression also indicated DNA damage. Western blot analysis revealed perturbation in expression of some DNA repair proteins including a large elevation of Rad51. Immunohistochemistry on clinical samples of PML showed robust labeling for Rad51 in nuclei of bizarre astrocytes and inclusion body-bearing oligodendrocytes that are characteristic of JCV infection. Finally, in vitro end-joining DNA repair was altered in extracts prepared from JCV-infected human astrocytes. Alterations in DNA repair pathways may be important for the life cycle of JCV and the pathogenesis of PML.
authors: Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, Philadelphia, PA 19122, USA.
authors: Armine
authors: A
authors: Darbinyan
authors: Martyn K
authors: MK
authors: White
authors: Selma
authors: S
authors: Akan
authors: Sujatha
authors: S
authors: Radhakrishnan
authors: Luis
authors: L
authors: Del Valle
authors: Shohreh
authors: S
authors: Amini
authors: Kamel
authors: K
authors: Khalili
mesh_terms: D000328:Adult; D001253:Astrocytes / Q000378:metabolism / Q000821:virology; D001483:Base Sequence; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D042822:Genomic Instability; D006801:Humans; D007577:JC Virus / Q000472:pathogenicity / Q000502:physiology; D007968:Leukoencephalopathy, Progressive Multifocal / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D051135:Rad51 Recombinase / Q000378:metabolism
chemical_list: D004247:DNA; C495153:RAD51 protein, human; D051135:Rad51 Recombinase