Secretome profiling of BK polyomavirus (BKPyV) infected cells: new clues to understand BKPyV persistence?
BK Polyomavirus (BKPyV) is a ubiquitous virus that establish a lifelong infection in the epithelial cells of the reno-urinary tract of >90% of humans worldwide. It rarely causes disease in healthy individuals but can cause nephropathy and premature graft failure in kidney transplant patients and haemorrhagic cystitis in bone-marrow transplant patients. There is no antiviral treatment available and the development of such treatment is hampered by the incomplete knowledge on the viral replication cycle. In addition, BKPyV is probably causing urothelial cancer in a small number of kidney transplant patients previously suffering from BKPyV-nephropathy.
The aim of this study was to gain deeper insights into BKPyV replication and the innate immune respond in persistently infected cells. We used the BKPyV-persistently infected U-2OS cell line denoted U-2OS15E1 and as a control the uninfected U-2OS cell line and compared their secretome. Three proteomic experiments were performed using isolated extracellular vesicles (EVs) from U-2OS15E and U-2OS and label-free LC-MS/MS. Moreover, free cytokines in the supernatants were analyzed by cytokine array. LC-MS/MS identified a total of 1747 proteins including 880 proteins enriched in EVs from U-2OS15E and 169 proteins enriched in EVs from U-2OS cells. One protein involved in innate immunity and cell death was found to be enriched and cleaved in EVs from U-2OS15E and was studied in more detail. The cytokine array revealed that only few cytokines were elevated in supernatants from U-2OS15E cells. The work is in progress.