TY - JOUR
T1 - SuPAR mediates viral response proteinuria by rapidly changing podocyte function
AU - Michigan Medicine COVID−19 Investigators
AU - Wei, Changli
AU - Datta, Prasun K.
AU - Siegerist, Florian
AU - Li, Jing
AU - Yashwanth, Sudhini
AU - Koh, Kwi Hye
AU - Kriho, Nicholas W.
AU - Ismail, Anis
AU - Luo, Shengyuan
AU - Fischer, Tracy
AU - Amber, Kyle T.
AU - Cimbaluk, David
AU - Landay, Alan
AU - Endlich, Nicole
AU - Rappaport, Jay
AU - Vasbinder, Alexi
AU - Anderson, Elizabeth
AU - Catalan, Tonimarie
AU - Pizzo, Ian
AU - Bitterman, Brayden
AU - Erne, Grace
AU - Machado-Diaz, Kristen
AU - Presswalla, Feriel
AU - Nelapudi, Namratha
AU - Amadi, Kingsley Michael
AU - Bardwell, Alina
AU - Blakely, Pennelope
AU - Huang, Yiyuan
AU - Banerjee, Mousumi
AU - Pop-Busui, Rodica
AU - Hayek, Salim S.
AU - Reiser, Jochen
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-023-40165-5
DO - 10.1038/s41467-023-40165-5
M3 - Article
C2 - 37479685
AN - SCOPUS:85165505551
SN - 2041-1723
VL - 14
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 4414
ER -