title: Transcriptional regulation of BK virus by nuclear factor of activated T cells.
abstract: The human polyomavirus BK virus (BKV) is a common virus for which 80 to 90% of the adult population is seropositive. BKV reactivation in immunosuppressed patients or renal transplant patients is the primary cause of polyomavirus-associated nephropathy (PVN). Using the Dunlop strain of BKV, we found that nuclear factor of activated T cells (NFAT) plays an important regulatory role in BKV infection. Luciferase reporter assays and chromatin immunoprecipitation assays demonstrated that NFAT4 bound to the viral promoter and regulated viral transcription and infection. The mutational analysis of the NFAT binding sites demonstrated complex functional interactions between NFAT, c-fos, c-jun, and the p65 subunit of NF-kappaB that together influence promoter activity and viral growth. These data indicate that NFAT is required for BKV infection and is involved in a complex regulatory network that both positively and negatively influences promoter activity and viral infection.
authors: Graduate Program in Pathobiology, Brown University, Providence, Rhode Island 02912, USA.
authors: Joslynn A
authors: JA
authors: Jordan
authors: Kate
authors: K
authors: Manley
authors: Aisling S
authors: AS
authors: Dugan
authors: Bethany A
authors: BA
authors: O'Hara
authors: Walter J
authors: WJ
authors: Atwood
mesh_terms: D000818:Animals; D001739:BK Virus / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002522:Chlorocebus aethiops; D017931:DNA Primers / Q000235:genetics; D005814:Genes, Viral; D006801:Humans; D009154:Mutation; D050778:NFATC Transcription Factors / Q000378:metabolism*; D027601:Polyomavirus Infections / Q000209:etiology; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D014412:Tumor Virus Infections / Q000209:etiology; D014709:Vero Cells
chemical_list: D017931:DNA Primers; D050778:NFATC Transcription Factors