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Journal Articles JCI Insight Year : 2023

A specific molecular signature in SARS-CoV-2 infected kidney biopsies

Franck Pourcine

Abstract

Acute kidney injury (AKI) is one of the most important complications in COVID-19 patients and is considered a negative prognostic factor with respect to patient survival. The occurrence of direct infection of the kidney by SARS-CoV-2, and its contribution to the renal deterioration process, remains a controversial issue. By studying 32 renal biopsies from COVID- 19 patients we confirmed that the major pathological feature of COVID-19 is acute tubular injury (ATI). Using smFISH, we showed that the SARS-CoV-2 infects living renal cells and that infection, which parallels renal ACE2 expression levels, is associated to increase death. Mechanistically, a transcriptomic analysis uncovered specific molecular signatures in SARS-CoV-2 infected kidneys as compared to healthy kidneys and non-COVID-19 ATI kidneys. On the other hand, we demonstrated that SARS-CoV-2 and Hantavirus, two RNA viruses, activated different genetic networks despite they triggered the same pathological lesions. Finally, we identified XAF1 as a critical target of SARS-CoV-2 infection. In conclusion, this study demonstrates that SARS-CoV2 can directly infect living renal cells and identified specific druggable molecular targets that can potentially aid in the design of novel therapeutic strategies to preserve renal function in severely affected COVID-19 patients.
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pasteur-04004769 , version 1 (25-02-2023)

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Pierre Isnard, Paul Vergnaud, Serge Garbay, Matthieu Jamme, Maeva Eloudzeri, et al.. A specific molecular signature in SARS-CoV-2 infected kidney biopsies. JCI Insight, In press, pp.e165192. ⟨10.1172/jci.insight.165192⟩. ⟨pasteur-04004769⟩
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