BK virus infection of renal epithelial cells is decreased by treatment with antagonist of Endothelin Receptor B

In recent years nephritis induced by BKvirus (BKV), non‐enveloped double‐strand deoxyribonucleic acid polyomavirus, has become a severe problem after renal transplantation. There is a critical need to better define the molecular mechanisms of BKV entry into its target cells and to develop efficient treatment strategies for BKV nephritis. Endothelins, agonists of G‐protein coupled receptors; act as important mediators of renal disease progression. Expression of endothelin receptors is markedly higher in proximal tubular epithelial cells in transplanted kidney. We have established that antagonist of Endothelin Receptor B (ETRB) BQ788 prevented BKV infection of cultured human renal proximal tubular epithelial cells (HRPTEC). The percentage of infected cells and the cellular levels of BKV large T antigen expression were significantly decreased in HRPTEC treated with BQ788, but not in HRPTEC treated with BQ123 (antagonist of Endothelin Receptor A). In order to confirm that BQ788 decreases BKV entry into HRPTEC we have analyzed distribution of Alexa Fluor 488 labeled BKV particles in HRPTEC after 4 hours incubation. We observed that in control HRPTEC labeled BKV particles were located mostly in the cytoplasm, whereas in HRPTEC treated with BQ788 a significant portion of BKV particles was located on the cell surface indicating that BQ788 interferes with entry pathway of BKV.