Glucocorticoids Do Not Enhance BK Polyomavirus Replication in Human Renal Proximal Tubular Epithelial Cells In Vitro

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Abstract
BK polyomavirus (BKPyV) infection may lead to BKPyV‐associated nephropathy (BKPyVAN) and subsequent graft loss in kidney transplant recipients. Experimental studies have suggested that glucocorticoids (GCs) may enhance BKPyV replication through a steroid‐responsive element within the viral genome. However, clinical observations have not consistently supported this association, prompting re‐investigation of the effect of GCs on BKPyV replication in primary human renal epithelial cells (PTECs). PTECs were infected with BKPyV and subsequently exposed to increasing concentrations of methylprednisolone (MPS) or dexamethasone (Dexa). Viral replication was quantified by quantitative polymerase chain reaction (qPCR). Relative differences in viral load were analyzed using univariate analysis of variance. Activation of the GC pathway was assessed by measuring FKBP5 and PER1 gene expression. Inflammatory responses were evaluated by enzyme‐linked immunosorbent assays (ELISA) for IL‐6, IL‐8, and TNF‐α. Treatment of BKPyV‐infected PTECs with increasing concentrations of MPS or Dexa did not affect viral replication compared to untreated controls. While treatment‐related changes in gene expression of FKBP5 and PER1 were observed, confirming GC‐signaling pathway activation in BKPyV‐infected cells. Cytokine production (IL‐6 and IL‐8) was unaffected. In primary human PTECs infected with BKPyV, treatment with MPS or Dexa did not enhance BKPyV replication. These findings contrast with earlier in vitro studies and suggest that glucocorticoids do not directly promote BKPyV replication under the conditions tested. Further studies are needed to determine whether these findings extend to other cell models and in vivo.

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