摘要：SummaryCOVID-19-associated acute kidney injury (COVID-AKI) is a common complication of SARS-CoV-2 infection in hospitalized patients. The susceptibility of human kidneys to direct SARS-CoV-2 infection and modulation of the renin-angiotensin II signaling (RAS) pathway by viral infection remain poorly characterized. Using induced pluripotent stem cell-derived kidney organoids, SARS-CoV-1, SARS-CoV-2, and MERS-CoV tropism, defined by the paired expression of a host receptor (ACE2,NRP1orDPP4) and protease (TMPRSS2,TMPRSS4,FURIN,CTSBorCTSL), was identified primarily among proximal tubule cells. Losartan, an angiotensin II receptor blocker being tested in patients with COVID-19, inhibited angiotensin II-mediated internalization of ACE2, upregulated interferon-stimulated genes (IFITM1andBST2) known to restrict viral entry, and attenuated the infection of proximal tubule cells by SARS-CoV-2. Our work highlights the susceptibility of proximal tubule cells to SARS-CoV-2 and reveals a putative protective role for RAS inhibitors during SARS-CoV-2 infection.Graphical abstractDisplay OmittedHighlights•SARS-CoV-2 kidney organoid tropism is primarily among proximal tubule cells•Losartan attenuates angiotensin II-mediated ACE2 internalization•Losartan upregulates viral restrictive genesIFITM1andBST2•SARS-CoV-2 infection is enhanced by angiotensin II and attenuated by losartanNephrology; Virology; Cell biology
