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SuPAR mediates viral response proteinuria by rapidly changing podocyte function

Author

Listed:
  • Changli Wei

    (Rush University Medical Center)

  • Prasun K. Datta

    (Tulane National Primate Research Center)

  • Florian Siegerist

    (University Medicine Greifswald
    NIPOKA GmbH)

  • Jing Li

    (Rush University Medical Center)

  • Sudhini Yashwanth

    (Rush University Medical Center)

  • Kwi Hye Koh

    (Morphic Therapeutic)

  • Nicholas W. Kriho

    (Rush University Medical Center)

  • Anis Ismail

    (University of Michigan)

  • Shengyuan Luo

    (Rush University Medical Center)

  • Tracy Fischer

    (Tulane National Primate Research Center)

  • Kyle T. Amber

    (Rush University Medical Center
    Rush University Medical Center)

  • David Cimbaluk

    (Rush University Medical Center)

  • Alan Landay

    (Rush University Medical Center)

  • Nicole Endlich

    (University Medicine Greifswald
    NIPOKA GmbH)

  • Jay Rappaport

    (Tulane National Primate Research Center)

  • Salim S. Hayek

    (University of Michigan)

  • Jochen Reiser

    (Rush University Medical Center)

Abstract

Elevation in soluble urokinase receptor (suPAR) and proteinuria are common signs in patients with moderate to severe coronavirus disease 2019 (COVID-19). Here we characterize a new type of proteinuria originating as part of a viral response. Inoculation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes increased suPAR levels and glomerulopathy in African green monkeys. Using an engineered mouse model with high suPAR expression, inhaled variants of SARS-CoV-2 spike S1 protein elicite proteinuria that could be blocked by either suPAR antibody or SARS-CoV-2 vaccination. In a cohort of 1991 COVID-19 patients, suPAR levels exhibit a stepwise association with proteinuria in non-Omicron, but not in Omicron infections, supporting our findings of biophysical and functional differences between variants of SARS-CoV-2 spike S1 protein and their binding to podocyte integrins. These insights are not limited to SARS-CoV-2 and define viral response proteinuria (VRP) as an innate immune mechanism and co-activation of podocyte integrins.

Suggested Citation

  • Changli Wei & Prasun K. Datta & Florian Siegerist & Jing Li & Sudhini Yashwanth & Kwi Hye Koh & Nicholas W. Kriho & Anis Ismail & Shengyuan Luo & Tracy Fischer & Kyle T. Amber & David Cimbaluk & Alan , 2023. "SuPAR mediates viral response proteinuria by rapidly changing podocyte function," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40165-5
    DOI: 10.1038/s41467-023-40165-5
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