title: DNA-binding transcription factor NF-1A negatively regulates JC virus multiplication.
abstract: JC virus (JCV) DNA replication occurs in the nuclei of infected cells. The level of JCV genome expression depends on nucleotide sequences in the viral regulatory region and their interaction with host-cell nuclear transcription factors. Our previous studies showed a higher level of NF-1X in JCV-permissive cells compared with the other members of the NF-1 family, NF-1A, B and C, which suggests that NF-1X plays a positive role in JCV multiplication. It remained unclear whether a reduction in the level of NF-1A, which is expressed abundantly in JCV-non-permissive cell types, leads to an increase in JCV multiplication. In this study, we show that downregulation of NF-1A expression in JCV-non-susceptible progenitor and HeLa cells results in a reversion to susceptibility for JCV multiplication. These data demonstrate that a higher level of NF-1A protein in JCV-non-permissive cell types, compared with the level of NF-1X, may be acting as a negative regulator at the JCV promoter to control JCV multiplication.
authors.affiliation: Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Veerasamy
authors.initials: V
authors.lastname: Ravichandran
authors.affiliation: Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Eugene O
authors.initials: EO
authors.lastname: Major
mesh_terms: D002467:Cell Nucleus / Q000821:virology; D002478:Cells, Cultured; D015536:Down-Regulation; D005333:Fetus; D006367:HeLa Cells; D006801:Humans; D007577:JC Virus / Q000502:physiology*; D051839:NFI Transcription Factors / Q000502:physiology*; D027601:Polyomavirus Infections / Q000821:virology*; D013234:Stem Cells; D013687:Telencephalon; D014412:Tumor Virus Infections / Q000821:virology*; D014779:Virus Replication
chemical_list: D051839:NFI Transcription Factors