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Nat Commun ; 14(1): 4414, 2023 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-37479685

RESUMO

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.


Assuntos
COVID-19 , Podócitos , Animais , Camundongos , Chlorocebus aethiops , Humanos , Vacinas contra COVID-19 , Receptores de Ativador de Plasminogênio Tipo Uroquinase/genética , SARS-CoV-2 , Integrinas , Proteinúria
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