BK polyomavirus early region pre-mRNA splice donor site (BKV early splice donor)

The BK polyomavirus early region pre-mRNA splice donor site is a critical regulatory element in the life cycle of the BK polyomavirus (BKV), a double-stranded DNA virus that remains latent in the urinary tract of most healthy individuals (Imperiale, 2001). Upon immunosuppression, particularly in kidney transplant recipients, BKV can reactivate, leading to BK polyomavirus-associated nephropathy (BKVAN) and potential graft loss (Hirsch & Randhawa, 2019). This specific splice donor site is responsible for the alternative splicing of the early pre-mRNA into transcripts for the Large T-antigen (LTA) and small t-antigen (stA) (Abend et al., 2007). The Large T-antigen is indispensable for viral DNA replication and the transition to the late phase of the viral cycle. Therapeutic strategies targeting this site, such as those developed by Aligos Therapeutics (e.g., ALG-059356), utilize antisense oligonucleotides (ASOs) to interfere with the splicing process or trigger the degradation of the viral transcript (Aligos Therapeutics, 2022). By preventing the synthesis of LTA, these drugs effectively halt viral replication and reduce the viral load in the host's renal tissues. This approach offers a highly specific method of viral inhibition compared to broad-spectrum antivirals. However, challenges remain regarding the efficient delivery of these oligonucleotides to the infected renal tubular epithelial cells and the potential for off-target effects on host RNA processing.

Other names

BKV early pre-mRNA 5' splice siteBK polyomavirus LTA/stA splice donor siteBKV early region 5'ssBK polyomavirus Large T-antigen splice donor

Antisense oligonucleotides bind to the splice donor site to sterically block the spliceosome or induce RNase H-mediated cleavage, thereby preventing the production of functional Large T-antigen mRNA and inhibiting viral replication.