Kidney organoids reveal redundancy in viral entry pathways during ACE2-dependent SARS-CoV-2 infection.

Jessica M VanslambrouckJessica A NeilRajeev RudrarajuSophia MahKer Sin TanElla GroenewegenThomas A ForbesKaterina KaravendzasDavid A ElliottEnzo R PorrelloKanta SubbaraoMelissa H Little

Published in: Journal of virology (2024)

Utilizing a human iPSC-derived kidney organoid model with improved proximal tubule (PT) maturity, we identified the mechanism of SARS-CoV-2 entry in renal cells, confirming ACE2 as the sole receptor and revealing redundancy in downstream cell surface TMPRSS- and endocytic Cathepsin-mediated pathways. In addition, these data address the implications of SARS-CoV-2 exposure in the setting of the commonly prescribed ACE-inhibitor, lisinopril, confirming its negligible impact on infection of kidney cells. Taken together, these results provide valuable insight into the mechanism of viral infection in the human kidney.

Keyphrases

sars cov
induced pluripotent stem cells
induced apoptosis
endothelial cells
respiratory syndrome coronavirus
cell cycle arrest
cell surface
angiotensin converting enzyme
angiotensin ii
pluripotent stem cells
endoplasmic reticulum stress
cell death
signaling pathway
cell proliferation
machine learning