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Kidney Week

Abstract: FR-PO732

Cellular Responses to BK Polyomavirus Infection in Transplanted Kidneys

Session Information

  • Transplantation: Basic
    November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

  • 2101 Transplantation: Basic

Authors

  • McCown, Phillip J., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States
  • Marvin, Tess A., Princeton University, Princeton, New Jersey, United States
  • Sealfon, Rachel S., Flatiron Institute, New York, New York, United States
  • Alakwaa, Fadhl, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States
  • Farkash, Evan A., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States
  • Otto, Edgar A., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States
  • Eichinger, Felix H., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States
  • Menon, Rajasree, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States
  • Berthier, Celine C., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States
  • Reed, Tavis Jahi, Princeton University, Princeton, New Jersey, United States
  • Arrowsmith, Paula Anne, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States
  • Shaffer, Kelly, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States
  • Imperiale, Michael, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States
  • Pipas, James M., University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Troyanskaya, Olga, Princeton University, Princeton, New Jersey, United States
  • Kretzler, Matthias, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States
  • Theesfeld, Chandra L., Princeton University, Princeton, New Jersey, United States
  • Naik, Abhijit S., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States
Background

BK virus (BKV) infection remains problematic following kidney transplantation. Despite delineation of tubular responses in cell culture, the effect of an immune system on the cell-specific response in vivo to BKV is less well-understood.

Methods

Single-cell RNA sequencing of kidney biopsies (12 surveillance, 5 peak viremia, and 9 resolving viremia) from the Michigan Human Kidney Transplant Transcriptomic Atlas study were analyzed for cell type-specific transcriptomic responses to viremia and viral nephropathy and compared with healthy surveillance biopsies and BKV infected cells in culture.

Results

BKV transcripts were found in tubular cells and immune cells, confirmed in lymphoid clusters by VP1 immunohistochemistry. Cytokine signaling, cell-cycle regulation, translation, and wound healing were activated in BKV-infected tubular cells but not in tubules of viremic patients without nephropathy where stress-signaling and immune response predominated. During peak viremia there was an expansion of adaptive but not innate immune response. BKV-infected tubules showed increased cytokine, interferon γ, and tumor necrosis factor (TNF) signaling in humans. In contrast, TNF signaling was reduced in cell cultures.

Conclusion

Differential transcriptional responses to BKV infection in vivo and in vitro highlight the complex cellular and immune crosstalk not captured in 2D models. These findings also point towards exploration of anti-TNF therapies for BKV.

Funding

  • NIDDK Support