The impact of everolimus on the BKV-associated oncogenesis

Purpose: Human polyomaviruse BK (BKV) has been considered as an oncogenic virus that may cause various human tumors. Considering that BKV is known to persist in urothelial cells and can reactivate in immunocompromised hosts, urothelial cell carcinoma is likely to be associated with BKV infection, especially in renal transplant patients (RTRs). However, the strategies regarding how to adjust immunosuppressant in RTRs and the role of everolimus (Evr) in BKV-associated oncogenesis are uncertain. Method: Using BKV-infected renal urothelial SV-HUC-1 cell models, we investigated the effect of Evr (a mammalian target of rapamycin [mTOR] inhibitor) on BKV inducing the normal urinary urothelial cell migration in vitro. After the infection of the SV-HUC-1 cells with BKV, the cells were then exposed to different concentrations of Evr. Results: We found that the infected SV-HUC-1 cells had transformed cell characteristics, such as increased colony formation, wound healing ability, migratory and invasion capacity, and MMP9 activity. Evr improved the transformation of the infected-SV HUC-1 cells by inhibiting the mTOR related pathway but not that of Ras signaling. Conclusion: In routine practice, mTOR inhibitors may be an ideal immunosuppressant for RTRs with BKV infection or urothelial cell carcinoma.