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 LittlePublished 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 apoptosis
- induced pluripotent stem cells
- endothelial cells
- respiratory syndrome coronavirus
- cell surface
- cell cycle arrest
- angiotensin converting enzyme
- angiotensin ii
- endoplasmic reticulum stress
- pluripotent stem cells
- single cell
- oxidative stress
- genome wide
- electronic health record
- dna methylation
- signaling pathway
- pi k akt
- binding protein
- cell proliferation