title: Activation of early gene transcription in polyomavirus BK by human immunodeficiency virus type 1 Tat.
abstract: Polyomavirus BK (BKV) is a serious problem for immunocompromised patients, where latent virus can enter into the lytic cycle causing cytolytic destruction of host cells. BKV infects >80% of the population worldwide during childhood and then remains in a latent state in the kidney. In the context of immunosuppression in kidney transplant patients, reactivation of the viral early promoter (BKV(E)) results in production of T antigen, enabling virus replication and transition from latency to the lytic phase, causing polyomavirus-associated nephropathy. Reactivation of BKV can also cause complications such as nephritis, atypical retinitis and haemorrhagic cystitis in AIDS patients. Here, the effects of human immunodeficiency virus type 1 (HIV-1) proteins Tat and Vpr on BKV transcription were investigated and it was demonstrated that Tat dramatically stimulated BKV(E). Site-directed mutagenesis analysis of potential Tat-responsive transcriptional motifs complemented by an electrophoretic mobility shift assay (EMSA) showed that Tat activated BKV(E) by inducing binding of the NF-kappaB p65 subunit to a kappaB motif near the 3' end of BKV(E). In addition, a sequence within the 5' UTR of BKV(E) transcripts (BKV(E)-TAR) was identified that is identical to the HIV-1 transactivation response (TAR) element. The BKV(E)-TAR sequence bound TAT in RNA EMSA assays and deletion of the BKV(E)-TAR sequence eliminated Tat transactivation of BKV(E) transcription. Thus, Tat positively affected BKV(E) transcription by a dual mechanism and this may be important in diseases involving BKV reactivation in AIDS patients.
authors.affiliation: Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, 1900 North 12th Street, 015-96, Room 203, Philadelphia, PA 19122, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Gorrill
authors.affiliation: Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, 1900 North 12th Street, 015-96, Room 203, Philadelphia, PA 19122, USA.
authors.forename: Mariha
authors.initials: M
authors.lastname: Feliciano
authors.affiliation: Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, 1900 North 12th Street, 015-96, Room 203, Philadelphia, PA 19122, USA.
authors.forename: Ruma
authors.initials: R
authors.lastname: Mukerjee
authors.affiliation: Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, 1900 North 12th Street, 015-96, Room 203, Philadelphia, PA 19122, USA.
authors.forename: Bassel E
authors.initials: BE
authors.lastname: Sawaya
authors.affiliation: Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, 1900 North 12th Street, 015-96, Room 203, Philadelphia, PA 19122, USA.
authors.forename: Kamel
authors.initials: K
authors.lastname: Khalili
authors.affiliation: Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, 1900 North 12th Street, 015-96, Room 203, Philadelphia, PA 19122, USA.
authors.forename: Martyn K
authors.initials: MK
authors.lastname: White
mesh_terms: D001739:BK Virus / Q000472:pathogenicity* / Q000502:physiology; D001483:Base Sequence; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D015696:Gene Products, tat / Q000378:metabolism*; D016336:Gene Products, vpr / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D016328:NF-kappa B / Q000737:chemistry / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014775:Virus Activation; D054322:tat Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus
chemical_list: D015696:Gene Products, tat; D016336:Gene Products, vpr; D016328:NF-kappa B; D014764:Viral Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus