Studies on the BK Polyomavirus Life Cycle and Virus- Induced Membrane Remodelling in Human Microvascular Endothelial Cells

Abstract

BK polyomavirus (BKPyV) is a small, nonenveloped human DNA virus that establisheslifelong, asymptomatic infections. However, it can reactivate underimmunosuppression, leading to severe diseases such as BKPyV-associatednephropathy. Human bladder microvascular endothelial cells (HBMVECs) have recentlybeen identified as viral reservoirs, while during virus reactivation, the primary targetbecome the proximal tubular epithelial cells (RPTECs). Interestingly, BKPyV mountsinterferon response in HBMVECs, but not after infection of RPTECs where the responseis halted likely due to mitochondrial damage induced by the viral agnoprotein. Wehypothesize, that the ability of reservoir cells to initiate antiviral response is dependenton interaction of the viral agnoprotein with cellular membranes in these cells. Our studythus uses HBMVECs model to investigate the molecular mechanisms of BKPyVreplication, cell architecture remodeling, and agnoprotein-membrane interactions. Toachieve this, we employed a range of imaging techniques including widefield, confocaland electron microscopy.