1887

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) 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. Site-directed mutagenesis analysis of potential Tat-responsive transcriptional motifs complemented by an electrophoretic mobility shift assay (EMSA) showed that Tat activated BKV by inducing binding of the NF-B p65 subunit to a B motif near the 3′ end of BKV. In addition, a sequence within the 5′ UTR of BKV transcripts (BKV-TAR) was identified that is identical to the HIV-1 transactivation response (TAR) element. The BKV-TAR sequence bound TAT in RNA EMSA assays and deletion of the BKV-TAR sequence eliminated Tat transactivation of BKV transcription. Thus, Tat positively affected BKV transcription by a dual mechanism and this may be important in diseases involving BKV reactivation in AIDS patients.

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2006-06-01
2021-05-14
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