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Activation of early gene transcription in polyomavirus BK by human immunodeficiency virus type 1 Tat

Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, 1900 North 12th Street, 015-96, Room 203, Philadelphia, PA 19122, USA

Correspondence
Martyn K. White
martyn.white{at}temple.edu

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-B p65 subunit to a B 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.

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