ArticleAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2016
BK Polyomavirus Replication in Renal Tubular Epithelial Cells Is Inhibited by Sirolimus, but Activated by Tacrolimus Through a Pathway Involving FKBP-12.
Article in American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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51 citing papers in PubMed, 126 citations in OpenAlex.
- Effects of two immunosuppression regimens on T-lymphocyte subsets in elderly kidney transplant recipients.Frontiers in immunology · 2024Trial
- Remodeling of the cellular membrane architecture in response to BK polyomavirus infection.Virology journal · 2026Review
- BK Nephropathy in the Modern Era: What Have We Learned?Kidney360 · 2025Review
- Donor Variability and PD-1 Expression Limit BK Polyomavirus-specific T-cell Function and Therapy.Transplantation · 2025Article
- Utility of the ELISpot Test to Predict the Risk of Developing BK Polyomavirus Nephropathy in Kidney Recipients, a Multicenter Study.Vaccines · 2025Article
- Regulatory T Cell in Kidney Transplant: The Future of Cell Therapy?Antibodies (Basel, Switzerland) · 2025Review
- BK Polyomavirus-associated nephropathy - diagnostic and treatment standard.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- The association between serum tacrolimus concentrations and BK viruria in kidney transplant recipients.Scientific reports · 2025Article
- Risk Prediction and Management of BKPyV-DNAemia in Kidney Transplant Recipients: A Multicenter Analysis of Immunosuppressive Strategies.Transplant international : official journal of the European Society for Organ Transplantation · 2025Article
- Single-cell RNA-sequencing of BK polyomavirus replication in primary human renal proximal tubular epithelial cells identifies specific transcriptome signatures and a novel mitochondrial stress pattern.Journal of virology · 2024Article
- Massive entry of BK Polyomavirus induces transient cytoplasmic vacuolization of human renal proximal tubule epithelial cells.PLoS pathogens · 2024Article
- Renal Allograft Function and the Tacrolimus C/D Ratio: Insights from a Prospective Study on MeltDose Tacrolimus.Journal of clinical medicine · 2024Article
- Pharmacodynamic Effect of mTOR Inhibition-based Immunosuppressive Therapy on T- and B-cell Subsets After Renal Transplantation.Transplantation direct · 2024Article
- A comparative analysis of clinical outcomes between conversion to mTOR inhibitor and calcineurin inhibitor reduction in managing BK viremia among kidney transplant patients.Scientific reports · 2024Article
- Association ofCurrent drug metabolism · 2024Article
- Molecular Characterization of BK Polyomavirus Replication in Allogeneic Hematopoietic Cell Transplantation Patients.The Journal of infectious diseases · 2023Article
- Conversion to mTOR-Inhibitors Plus IV Immunoglobulins in Kidney-Transplant Recipients with BKV Infection: A Retrospective Comparative Study.Journal of clinical medicine · 2022Article
- IFNL4 rs368234815 polymorphism does not predict risk of BK virus associated nephropathy after living-donor kidney transplant: A case-control study.Clinical transplantation · 2022Article
- Adverse Effects of Immunosuppression: Infections.Handbook of experimental pharmacology · 2022Article
- Proteomic analysis of urinary extracellular vesicles of kidney transplant recipients with BKV viruria and viremia: A pilot study.Frontiers in medicine · 2022Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BK polyomavirus (BKPyV) replication causes nephropathy and premature kidney transplant failure. Insufficient BKPyV-specific T cell control is regarded as a key mechanism, but direct effects of immunosuppressive drugs on BKPyV replication might play an additional role. We compared the effects of mammalian target of rapamycin (mTOR)- and calcineurin-inhibitors on BKPyV replication in primary human renal tubular epithelial cells. Sirolimus impaired BKPyV replication with a 90% inhibitory concentration of 4 ng/mL by interfering with mTOR-SP6-kinase activation. Sirolimus inhibition was rapid and effective up to 24 h postinfection during viral early gene expression, but not thereafter, during viral late gene expression. The mTORC-1 kinase inhibitor torin-1 showed a similar inhibition profile, supporting the notion that early steps of BKPyV replication depend on mTOR activity. Cyclosporine A also inhibited BKPyV replication, while tacrolimus activated BKPyV replication and reversed sirolimus inhibition. FK binding protein 12kda (FKBP-12) siRNA knockdown abrogated sirolimus inhibition and increased BKPyV replication similar to adding tacrolimus. Thus, sirolimus and tacrolimus exert opposite effects on BKPyV replication in renal tubular epithelial cells by a mechanism involving FKBP-12 as common target. Immunosuppressive drugs may therefore contribute directly to the risk of BKPyV replication and nephropathy besides suppressing T cell functions. The data provide rationales for clinical trials aiming at reducing the risk of BKPyV replication and disease in kidney transplantation.
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