title: T-antigen-dependent transcriptional initiation and its role in the regulation of human neurotropic JC virus late gene expression.
abstract: The multifunctional protein of papovaviruses, T-antigen, regulates the virus lytic cycle partly by exerting transcriptional control over viral and cellular gene expression. In this study, the ability of the T-antigen of human neurotropic JC virus (JCV) to enhance expression from the virus late promoter has been further examined. By deletion analysis, a T-antigen-responsive region was mapped within the JCV 98 bp enhancer/promoter between nucleotides 139 and 168. Interestingly, T-antigen appears to mediate transactivation by increasing expression from a basal transcriptional initiation site and through a novel T-antigen-dependent initiation site (TADI). The TADI element contains a region homologous to initiator (Inr) sequences and is sufficient to confer T-antigen responsiveness to a heterologous minimal promoter. Electrophoretic mobility shift and UV crosslinking analyses demonstrate that multiple cellular proteins interact with both single- and double-stranded forms of this sequence. Mutations within the TADI element which abolish T-antigen-mediated transcriptional activation also prevent the formation of specific nucleoprotein complexes. These data suggest that the ability of JCV T-antigen to regulate JCV late gene expression may be partly due to the formation of specific nucleoprotein complexes and transcriptional initiation from the TADI site on the viral promoter.
authors.affiliation: Center for NeuroVirology and NeuroOncology, Allegheny University of the Health Sciences, Philadelphia, PA 19102, USA.
authors.forename: G V
authors.initials: GV
authors.lastname: Raj
authors.forename: G L
authors.initials: GL
authors.lastname: Gallia
authors.forename: C F
authors.initials: CF
authors.lastname: Chang
authors.forename: K
authors.initials: K
authors.lastname: Khalili
mesh_terms: D000957:Antigens, Viral, Tumor / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D006367:HeLa Cells; D006801:Humans; D007577:JC Virus / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D009154:Mutation; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D011401:Promoter Regions, Genetic; D017384:Sequence Deletion; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D000957:Antigens, Viral, Tumor; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides