BK polyomavirus small T antigen (sT)

BK polyomavirus small T antigen (sT) is a critical early regulatory protein encoded by the BK polyomavirus (BKPyV), a double-stranded DNA virus that establishes lifelong persistent infection in the majority of the human population. The sT protein primarily functions by hijacking host cell signaling, most notably through its high-affinity interaction with the Protein Phosphatase 2A (PP2A) enzyme complex. By binding to the PP2A scaffold and catalytic subunits, sT displaces regulatory B subunits, thereby altering phosphatase activity to favor cell cycle progression into the S phase, which provides the necessary machinery for viral DNA replication. In addition to its role in the viral life cycle, sT contributes to cellular transformation and is considered an oncoprotein. In immunocompromised patients, particularly renal transplant recipients, the reactivation of BKPyV leads to severe clinical conditions such as BK polyomavirus-associated nephropathy (BKVAN) and hemorrhagic cystitis. While sT is essential for viral persistence and host cell manipulation, there are currently no FDA-approved drugs that specifically target this protein. Current clinical management relies on reducing immunosuppression or using off-label antivirals like cidofovir and leflunomide, which target viral DNA polymerase or host pyrimidine synthesis rather than sT itself. Research into small molecules that disrupt the sT-PP2A interface remains a significant area of interest for developing targeted anti-polyomavirus therapies.

Other names

Small t antigenBKPyV sTBKPyV tAgSmall tumor antigenEarly protein STST-AG