title: Glial cell type-specific subcellular localization of 14-3-3 zeta: an implication for JCV tropism.
abstract: 14-3-3 Isoforms are shown to be upregulated or accumulated in the glial cells of autopsied patient brains affected with progressive multifocal leukoencephalopathy (PML), a demylinating disease caused by JC virus (JCV). The possible involvement of 14-3-3 in JCV tropism, however, has never been examined. To investigate a potential relationship between 14-3-3 isoforms and JCV in vitro, we examined the localization of six 14-3-3 isoforms in human neural progenitors and progenitor-derived astrocytes (PDAs) in cells without JCV exposure. The 14-3-3 zeta isoform was initially localized in the progenitor cytoplasm. When differentiation of progenitors into PDAs was induced, the zeta isoform was translocated into the nucleus. However, upon JCV infection, progenitor cells exhibited an uncharacteristic 14-3-3 zeta nuclear presence in the few cells that became infected. JCV-treated PDAs showed elevated levels of 14-3-3 zeta compared with noninfected PDAs. Treatment with TGF-beta1, a known stimulant of JCV multiplication, increased the overall number of infected cells and the otherwise absent nuclear presence of 14-3-3 zeta in progenitors. These results suggest that the nuclear presence of 14-3-3 zeta may play a role in JCV infection, and that the isoform may in part determine JCV susceptibility in these cell types.
authors.affiliation: Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1296, USA.
authors.forename: Shivani
authors.initials: S
authors.lastname: Lamba
authors.forename: Veerasamy
authors.initials: V
authors.lastname: Ravichandran
authors.forename: Eugene O
authors.initials: EO
authors.lastname: Major
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D021581:Active Transport, Cell Nucleus; D001253:Astrocytes / Q000378:metabolism* / Q000821:virology; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism / Q000821:virology; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D006801:Humans; D007118:Immunoassay; D007577:JC Virus / Q000502:physiology*; D009474:Neurons / Q000378:metabolism* / Q000821:virology; D013234:Stem Cells / Q000378:metabolism* / Q000821:virology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D048948:14-3-3 Proteins; D053773:Transforming Growth Factor beta1