Uncovering agnoprotein interactions with cellular membranes during BKPyV infection in reservoir cells

Abstract

BK polyomavirus (BKPyV), a widespread human virus, causes asymptomatic infectionsthat persist indefinitely. In immunosuppressed patients, particularly kidney transplantrecipients, reactivated viral replication can lead to nephropathy and graft loss. TheBKPyV genome encodes structural capsid proteins and multifunctional regulatoryproteins, including T antigens and agnoprotein. While most of the viral proteins are wellcharacterised, the role of agnoprotein remains unclear, although it is thought tocontribute to the release of viral progeny. Agnoprotein is also known to interact with hostcell membranes due to its hydrophobic nature. In the past, in vitro studies of the BKPyVinfection have predominantly utilized renal proximal tubular epithelial kidney cells(RPTECs), which are the primary targets during viral reactivation. Recently, humanbladder microvascular endothelial cells (HBMVECs) have been identified as a potentialviral reservoir. The observation that BKPyV elicits different responses in RPTECs andHBMVECs, has led us to hypothesise that understanding the behaviour of the virus inreservoir cells may provide key insights into its mechanisms of persistence.