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Clinical Research and Public HealthIn-Press PreviewImmunologyNephrologyVirology Open Access | 10.1172/jci.insight.198227

Single-cell Analysis of Human Kidney Biopsy Tissue Reveals Epithelial and Immune Cell Responses to BK Polyomavirus Infection

Tess Marvin,1 Rachel Sealfon,2 Phillip J. McCown,3 Fadhl AlAkwaa,3 Evan A. Farkash,4 Edgar A. Otto,3 Felix Eichinger,3 Ping An,5 Rajasree Menon,6 Celine C. Berthier,3 Tavis J. Reed,1 Paula Arrowsmith,4 Lalita Subramanian,7 Kelly J. Shaffer,3 Silas P. Norman,3 Ramnika Gumber,3 Michael J. Imperiale,8 James M. Pipas,5 Olga G. Troyanskaya,1 Matthias Kretzler,3 Chandra L. Theesfeld,1 and Abhijit S. Naik3

1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United States of America

2Center for Computational Biology, Flatiron Institute, New York, United States of America

3Division of Nephrology, University of Michigan, Ann Arbor, United States of America

4Department of Pathology, University of Michigan, Ann Arbor, United States of America

5Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States of America

6Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, United States of America

7Division of Nephrology, University of Michiagn, Ann Arbor, United States of America

8Department of Microbiology, University of Michigan, Ann Arbor, United States of America

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1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United States of America

2Center for Computational Biology, Flatiron Institute, New York, United States of America

3Division of Nephrology, University of Michigan, Ann Arbor, United States of America

4Department of Pathology, University of Michigan, Ann Arbor, United States of America

5Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States of America

6Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, United States of America

7Division of Nephrology, University of Michiagn, Ann Arbor, United States of America

8Department of Microbiology, University of Michigan, Ann Arbor, United States of America

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1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United States of America

2Center for Computational Biology, Flatiron Institute, New York, United States of America

3Division of Nephrology, University of Michigan, Ann Arbor, United States of America

4Department of Pathology, University of Michigan, Ann Arbor, United States of America

5Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States of America

6Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, United States of America

7Division of Nephrology, University of Michiagn, Ann Arbor, United States of America

8Department of Microbiology, University of Michigan, Ann Arbor, United States of America

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1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United States of America

2Center for Computational Biology, Flatiron Institute, New York, United States of America

3Division of Nephrology, University of Michigan, Ann Arbor, United States of America

4Department of Pathology, University of Michigan, Ann Arbor, United States of America

5Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States of America

6Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, United States of America

7Division of Nephrology, University of Michiagn, Ann Arbor, United States of America

8Department of Microbiology, University of Michigan, Ann Arbor, United States of America

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1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United States of America

2Center for Computational Biology, Flatiron Institute, New York, United States of America

3Division of Nephrology, University of Michigan, Ann Arbor, United States of America

4Department of Pathology, University of Michigan, Ann Arbor, United States of America

5Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States of America

6Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, United States of America

7Division of Nephrology, University of Michiagn, Ann Arbor, United States of America

8Department of Microbiology, University of Michigan, Ann Arbor, United States of America

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1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United States of America

2Center for Computational Biology, Flatiron Institute, New York, United States of America

3Division of Nephrology, University of Michigan, Ann Arbor, United States of America

4Department of Pathology, University of Michigan, Ann Arbor, United States of America

5Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States of America

6Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, United States of America

7Division of Nephrology, University of Michiagn, Ann Arbor, United States of America

8Department of Microbiology, University of Michigan, Ann Arbor, United States of America

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1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United States of America

2Center for Computational Biology, Flatiron Institute, New York, United States of America

3Division of Nephrology, University of Michigan, Ann Arbor, United States of America

4Department of Pathology, University of Michigan, Ann Arbor, United States of America

5Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States of America

6Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, United States of America

7Division of Nephrology, University of Michiagn, Ann Arbor, United States of America

8Department of Microbiology, University of Michigan, Ann Arbor, United States of America

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1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United States of America

2Center for Computational Biology, Flatiron Institute, New York, United States of America

3Division of Nephrology, University of Michigan, Ann Arbor, United States of America

4Department of Pathology, University of Michigan, Ann Arbor, United States of America

5Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States of America

6Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, United States of America

7Division of Nephrology, University of Michiagn, Ann Arbor, United States of America

8Department of Microbiology, University of Michigan, Ann Arbor, United States of America

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1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United States of America

2Center for Computational Biology, Flatiron Institute, New York, United States of America

3Division of Nephrology, University of Michigan, Ann Arbor, United States of America

4Department of Pathology, University of Michigan, Ann Arbor, United States of America

5Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States of America

6Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, United States of America

7Division of Nephrology, University of Michiagn, Ann Arbor, United States of America

8Department of Microbiology, University of Michigan, Ann Arbor, United States of America

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1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United States of America

2Center for Computational Biology, Flatiron Institute, New York, United States of America

3Division of Nephrology, University of Michigan, Ann Arbor, United States of America

4Department of Pathology, University of Michigan, Ann Arbor, United States of America

5Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States of America

6Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, United States of America

7Division of Nephrology, University of Michiagn, Ann Arbor, United States of America

8Department of Microbiology, University of Michigan, Ann Arbor, United States of America

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1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United States of America

2Center for Computational Biology, Flatiron Institute, New York, United States of America

3Division of Nephrology, University of Michigan, Ann Arbor, United States of America

4Department of Pathology, University of Michigan, Ann Arbor, United States of America

5Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States of America

6Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, United States of America

7Division of Nephrology, University of Michiagn, Ann Arbor, United States of America

8Department of Microbiology, University of Michigan, Ann Arbor, United States of America

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1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United States of America

2Center for Computational Biology, Flatiron Institute, New York, United States of America

3Division of Nephrology, University of Michigan, Ann Arbor, United States of America

4Department of Pathology, University of Michigan, Ann Arbor, United States of America

5Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States of America

6Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, United States of America

7Division of Nephrology, University of Michiagn, Ann Arbor, United States of America

8Department of Microbiology, University of Michigan, Ann Arbor, United States of America

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1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United States of America

2Center for Computational Biology, Flatiron Institute, New York, United States of America

3Division of Nephrology, University of Michigan, Ann Arbor, United States of America

4Department of Pathology, University of Michigan, Ann Arbor, United States of America

5Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States of America

6Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, United States of America

7Division of Nephrology, University of Michiagn, Ann Arbor, United States of America

8Department of Microbiology, University of Michigan, Ann Arbor, United States of America

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1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United States of America

2Center for Computational Biology, Flatiron Institute, New York, United States of America

3Division of Nephrology, University of Michigan, Ann Arbor, United States of America

4Department of Pathology, University of Michigan, Ann Arbor, United States of America

5Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States of America

6Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, United States of America

7Division of Nephrology, University of Michiagn, Ann Arbor, United States of America

8Department of Microbiology, University of Michigan, Ann Arbor, United States of America

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1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United States of America

2Center for Computational Biology, Flatiron Institute, New York, United States of America

3Division of Nephrology, University of Michigan, Ann Arbor, United States of America

4Department of Pathology, University of Michigan, Ann Arbor, United States of America

5Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States of America

6Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, United States of America

7Division of Nephrology, University of Michiagn, Ann Arbor, United States of America

8Department of Microbiology, University of Michigan, Ann Arbor, United States of America

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1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United States of America

2Center for Computational Biology, Flatiron Institute, New York, United States of America

3Division of Nephrology, University of Michigan, Ann Arbor, United States of America

4Department of Pathology, University of Michigan, Ann Arbor, United States of America

5Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States of America

6Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, United States of America

7Division of Nephrology, University of Michiagn, Ann Arbor, United States of America

8Department of Microbiology, University of Michigan, Ann Arbor, United States of America

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1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United States of America

2Center for Computational Biology, Flatiron Institute, New York, United States of America

3Division of Nephrology, University of Michigan, Ann Arbor, United States of America

4Department of Pathology, University of Michigan, Ann Arbor, United States of America

5Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States of America

6Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, United States of America

7Division of Nephrology, University of Michiagn, Ann Arbor, United States of America

8Department of Microbiology, University of Michigan, Ann Arbor, United States of America

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1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United States of America

2Center for Computational Biology, Flatiron Institute, New York, United States of America

3Division of Nephrology, University of Michigan, Ann Arbor, United States of America

4Department of Pathology, University of Michigan, Ann Arbor, United States of America

5Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States of America

6Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, United States of America

7Division of Nephrology, University of Michiagn, Ann Arbor, United States of America

8Department of Microbiology, University of Michigan, Ann Arbor, United States of America

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1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United States of America

2Center for Computational Biology, Flatiron Institute, New York, United States of America

3Division of Nephrology, University of Michigan, Ann Arbor, United States of America

4Department of Pathology, University of Michigan, Ann Arbor, United States of America

5Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States of America

6Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, United States of America

7Division of Nephrology, University of Michiagn, Ann Arbor, United States of America

8Department of Microbiology, University of Michigan, Ann Arbor, United States of America

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1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United States of America

2Center for Computational Biology, Flatiron Institute, New York, United States of America

3Division of Nephrology, University of Michigan, Ann Arbor, United States of America

4Department of Pathology, University of Michigan, Ann Arbor, United States of America

5Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States of America

6Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, United States of America

7Division of Nephrology, University of Michiagn, Ann Arbor, United States of America

8Department of Microbiology, University of Michigan, Ann Arbor, United States of America

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1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United States of America

2Center for Computational Biology, Flatiron Institute, New York, United States of America

3Division of Nephrology, University of Michigan, Ann Arbor, United States of America

4Department of Pathology, University of Michigan, Ann Arbor, United States of America

5Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States of America

6Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, United States of America

7Division of Nephrology, University of Michiagn, Ann Arbor, United States of America

8Department of Microbiology, University of Michigan, Ann Arbor, United States of America

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1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, United States of America

2Center for Computational Biology, Flatiron Institute, New York, United States of America

3Division of Nephrology, University of Michigan, Ann Arbor, United States of America

4Department of Pathology, University of Michigan, Ann Arbor, United States of America

5Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States of America

6Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, United States of America

7Division of Nephrology, University of Michiagn, Ann Arbor, United States of America

8Department of Microbiology, University of Michigan, Ann Arbor, United States of America

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Published March 12, 2026 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.198227.
Copyright © 2026, Marvin et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published March 12, 2026 - Version history
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Abstract

Introduction: BK polyomavirus (BKV) infection is associated with injury and subsequent graft loss due to the extent of injury or rejection. However, the molecular mechanisms driving injury and subsequent adverse outcomes remain poorly understood. Methods: In a cross-sectional study, single-cell RNA sequencing from kidney allograft biopsies was used to assess cell type-specific responses between uninfected controls and two distinct phases of BKV infection: peaking (increasing viral blood titers) and resolving (decreasing viral titers following immunosuppression reduction). Results: Genes upregulated in BK viral nephropathy (BKVN) were enriched for polyomavirus infection hallmarks, including ribosome biogenesis, translation, and energy restructuring. Additionally enriched pathways included wound healing, cellular stress, antigen presentation and immune signaling. Even without BKVN (peaking BK viremia alone), epithelial cells expressed signatures for wound healing, cellular stress, and extracellular matrix remodeling. In vivo tubular cell responses at single-cell resolution were validated against single cell transcriptomic data of BKV infected cells in a cell culture model. Despite similarities, in vivo tubular cells underwent metabolic adaptation favoring fatty acid oxidation and proinflammatory responses not observed in culture models likely due to an absent innate and adaptive immune system. Despite lymphopenia and immunosuppressive therapies, the proportion of recipient derived intrarenal adaptive immune cells was increased in biopsies associated with peaking viremia alongside activation of innate immune responses. Adaptive immune cells exhibited persistent inflammatory signaling and remodeling of energy metabolism during the resolving phase of infection. Conclusion: These not previously reported insights into BKV-associated injury may have implications for clinical management and improved allograft outcomes.

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