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

Phillip J. McCown,

• Marvin, Tess A., Princeton University, Princeton, New Jersey, United States

Tess A. Marvin,

• Sealfon, Rachel S., Flatiron Institute, New York, New York, United States

Rachel S. Sealfon,

• Alakwaa, Fadhl, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Fadhl Alakwaa,

• Farkash, Evan A., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Evan A. Farkash,

• Otto, Edgar A., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Edgar A. Otto,

• Eichinger, Felix H., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Felix H. Eichinger,

• Menon, Rajasree, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Rajasree Menon,

• Berthier, Celine C., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Celine C. Berthier,

• Reed, Tavis Jahi, Princeton University, Princeton, New Jersey, United States

Tavis Jahi Reed,

• Arrowsmith, Paula Anne, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Paula Anne Arrowsmith,

• Shaffer, Kelly, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Kelly Shaffer,

• Imperiale, Michael, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Michael Imperiale,

• Pipas, James M., University of Pittsburgh, Pittsburgh, Pennsylvania, United States

James M. Pipas,

• Troyanskaya, Olga, Princeton University, Princeton, New Jersey, United States

Olga Troyanskaya,

• Kretzler, Matthias, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Matthias Kretzler,

• Theesfeld, Chandra L., Princeton University, Princeton, New Jersey, United States

Chandra L. Theesfeld,

• Naik, Abhijit S., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Abhijit S. Naik,

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