SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids.
COVID-19
SARS-CoV-2
chronic kidney disease
fibrosis
human iPSC kidney organoids
kidney injury
protease blocker
Journal
Cell stem cell
ISSN: 1875-9777
Titre abrégé: Cell Stem Cell
Pays: United States
ID NLM: 101311472
Informations de publication
Date de publication:
03 02 2022
03 02 2022
Historique:
received:
28
02
2021
revised:
03
09
2021
accepted:
16
12
2021
pubmed:
16
1
2022
medline:
10
2
2022
entrez:
15
1
2022
Statut:
ppublish
Résumé
Kidney failure is frequently observed during and after COVID-19, but it remains elusive whether this is a direct effect of the virus. Here, we report that SARS-CoV-2 directly infects kidney cells and is associated with increased tubule-interstitial kidney fibrosis in patient autopsy samples. To study direct effects of the virus on the kidney independent of systemic effects of COVID-19, we infected human-induced pluripotent stem-cell-derived kidney organoids with SARS-CoV-2. Single-cell RNA sequencing indicated injury and dedifferentiation of infected cells with activation of profibrotic signaling pathways. Importantly, SARS-CoV-2 infection also led to increased collagen 1 protein expression in organoids. A SARS-CoV-2 protease inhibitor was able to ameliorate the infection of kidney cells by SARS-CoV-2. Our results suggest that SARS-CoV-2 can directly infect kidney cells and induce cell injury with subsequent fibrosis. These data could explain both acute kidney injury in COVID-19 patients and the development of chronic kidney disease in long COVID.
Identifiants
pubmed: 35032430
pii: S1934-5909(21)00520-8
doi: 10.1016/j.stem.2021.12.010
pmc: PMC8709832
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
217-231.e8Investigateurs
Hagit Achdout
(H)
Anthony Aimon
(A)
Elad Bar-David
(E)
Haim Barr
(H)
Amir Ben-Shmuel
(A)
James Bennett
(J)
Melissa L Boby
(ML)
Bruce Borden
(B)
Gregory R Bowman
(GR)
Juliane Brun
(J)
Sarma Bvnbs
(S)
Mark Calmiano
(M)
Anna Carbery
(A)
Emma Cattermole
(E)
Eugene Chernychenko
(E)
John D Choder
(JD)
Austin Clyde
(A)
Joseph E Coffland
(JE)
Galit Cohen
(G)
Jason Cole
(J)
Alessandro Contini
(A)
Lisa Cox
(L)
Milan Cvitkovic
(M)
Alex Dias
(A)
Kim Donckers
(K)
David L Dotson
(DL)
Alica Douangamath
(A)
Shirly Duberstein
(S)
Tim Dudgeon
(T)
Louise Dunnett
(L)
Peter K Eastman
(PK)
Noam Erez
(N)
Charles J Eyermann
(CJ)
Mike Fairhead
(M)
Gwen Fate
(G)
Daren Fearon
(D)
Oleg Federov
(O)
Matteo Ferla
(M)
Rafaela S Fernandes
(RS)
Lori Ferrins
(L)
Richard Foster
(R)
Holly Foster
(H)
Ronen Gabizon
(R)
Adolfo Garcia-Sastre
(A)
Victor O Gawriljuk
(VO)
Paul Gehrtz
(P)
Carina Gileadi
(C)
Charline Giroud
(C)
William G Glass
(WG)
Robert Glen
(R)
None Itai Glinert
Andre S Godoy
(AS)
Marian Gorichko
(M)
Tyler Gorrie-Stone
(T)
Ed J Griffen
(EJ)
Storm Hassell Hart
(SH)
Jag Heer
(J)
Micheal Henry
(M)
Michelle Hill
(M)
Sam Horrell
(S)
Matthew F D Hurley
(MFD)
Tomer Israely
(T)
Andrew Jajack
(A)
Eric Jnoff
(E)
Dirk Jochmans
(D)
Tobias John
(T)
Steven De Jonghe
(S)
Anastassia L Kantsadi
(AL)
Peter W Kenny
(PW)
J L Kiappes
(JL)
Lizbe Koekemoer
(L)
Boris Kovar
(B)
Tobias Krojer
(T)
Alpha A Lee
(AA)
Bruce A Lefker
(BA)
Haim Levy
(H)
Nir London
(N)
Petra Lukacik
(P)
Hannah Bruce Macdonald
(HB)
Beth Maclean
(B)
Tika R Malla
(TR)
Tatiana Matviiuk
(T)
Willam McCorkindale
(W)
Briana L McGovern
(BL)
Sharon Melamed
(S)
Oleg Michurin
(O)
Halina Mikolajek
(H)
Bruce F Milne
(BF)
Aaron Morris
(A)
Garret M Morris
(GM)
Melody Jane Morwitzer
(MJ)
Demetri Moustakas
(D)
Aline M Nakamura
(AM)
Jose Brandao Neto
(JB)
Johan Neyts
(J)
Luong Nguyen
(L)
Gabriela D Noske
(GD)
Vladas Oleinikovas
(V)
Glaucius Oliva
(G)
Gijs J Overheul
(GJ)
David Owen
(D)
Vladimir Psenak
(V)
Ruby Pai
(R)
Jin Pan
(J)
Nir Paran
(N)
Benjamin Perry
(B)
Maneesh Pingle
(M)
Jakir Pinjari
(J)
Boaz Politi
(B)
Ailsa Powell
(A)
Reut Puni
(R)
Victor L Rangel
(VL)
Ranbabu N Reddi
(RN)
St Patrick Reid
(SP)
Efrat Resnick
(E)
Emily Grace Ripka
(EG)
Matthew C Robinson
(MC)
Ralph P Robinson
(RP)
Jaime Rodriguez-Guerra
(J)
Romel Rosales
(R)
Dominic Rufa
(D)
Chris Schofield
(C)
Mikhail Shafeev
(M)
Aarif Shaikh
(A)
Jiye Shi
(J)
Khriesto Shurrush
(K)
Sukrit Sing
(S)
Assa Sittner
(A)
Rachael Skyner
(R)
Adam Smalley
(A)
Mihaela D Smilova
(MD)
Leonardo J Solmesky
(LJ)
John Spencer
(J)
Claire Strain-Damarell
(C)
Vishwanath Swamy
(V)
Hadas Tamir
(H)
Rachael Tennant
(R)
Warren Thompson
(W)
Andrew Thompson
(A)
Warren Thompson
(W)
Susana Tomasia
(S)
Anthony Tumber
(A)
Ioannis Vakonakis
(I)
Ronald P van Rij
(RP)
Laura van Geel
(L)
Finny S Varghese
(FS)
Mariana Vaschetto
(M)
Einat B Vitner
(EB)
Vincent Voelz
(V)
Andra Volkamer
(A)
Frank von Delft
(F)
Annette von Delft
(A)
Martin Walsh
(M)
Walter Ward
(W)
Charlie Weatherall
(C)
Shay Weiss
(S)
Kris M White
(KM)
Conor Francis Wild
(CF)
Matthew Wittmann
(M)
Nathan Wright
(N)
Yfat Yahalom-Ronen
(Y)
Daniel Zaidmann
(D)
Hadeer Zidane
(H)
Nicole Zitzmann
(N)
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
Références
J Am Soc Nephrol. 2016 Sep;27(9):2658-69
pubmed: 26823548
Eur J Pharmacol. 2016 Nov 5;790:62-73
pubmed: 27448504
Redox Biol. 2019 Sep;26:101302
pubmed: 31442911
Front Immunol. 2020 Jul 07;11:1346
pubmed: 32733450
Liver Int. 2020 Jul;40(7):1590-1593
pubmed: 32369658
Cell Stem Cell. 2020 Dec 3;27(6):951-961.e5
pubmed: 33113348
Methods Cell Biol. 2021;162:115-149
pubmed: 33707009
Nat Methods. 2019 Jan;16(1):79-87
pubmed: 30573816
Kidney Int. 2017 Oct;92(4):888-899
pubmed: 28483378
Nephrol Dial Transplant. 2006 Feb;21(2):288-98
pubmed: 16249193
Lancet. 2020 Aug 29;396(10251):597-598
pubmed: 32818439
N Engl J Med. 2020 Aug 6;383(6):590-592
pubmed: 32402155
J Am Soc Nephrol. 2021 Nov;32(11):2851-2862
pubmed: 34470828
Nat Med. 2013 Aug;19(8):1047-53
pubmed: 23817022
J Clin Invest. 2014 Jun;124(6):2299-306
pubmed: 24892703
Sci Rep. 2020 Oct 9;10(1):16944
pubmed: 33037310
Crit Care. 2021 Jan 25;25(1):37
pubmed: 33494766
Science. 2015 Jan 23;347(6220):1260419
pubmed: 25613900
Nat Rev Nephrol. 2021 Mar;17(3):172-184
pubmed: 32989282
Histopathology. 2021 Feb;78(3):358-370
pubmed: 32981112
Nat Commun. 2021 Apr 13;12(1):2190
pubmed: 33850129
Nature. 2018 Nov;563(7731):347-353
pubmed: 30429548
J Cell Biochem. 2015 Sep;116(9):1880-7
pubmed: 25727481
Kidney Int. 2011 Apr;79(8):861-70
pubmed: 21270764
Euro Surveill. 2020 Jan;25(3):
pubmed: 31992387
Nature. 2021 Jan;589(7841):281-286
pubmed: 33176333
Nat Protoc. 2016 Sep;11(9):1681-92
pubmed: 27560173
Cell. 2006 Aug 25;126(4):663-76
pubmed: 16904174
J Am Soc Nephrol. 2017 Nov;28(11):3166-3174
pubmed: 28864466
Cancer Res. 2018 Feb 1;78(3):769-780
pubmed: 29229604
J Clin Invest. 2015 Aug 3;125(8):2935-51
pubmed: 26193634
Physiol Genomics. 2021 Jan 1;53(1):1-11
pubmed: 33197228
Viruses. 2014 Aug 07;6(8):2991-3018
pubmed: 25105276
Nat Genet. 2016 Aug;48(8):838-47
pubmed: 27322546
Mediators Inflamm. 2018 Dec 23;2018:8739473
pubmed: 30670929
OMICS. 2012 May;16(5):284-7
pubmed: 22455463
Nature. 2015 Oct 22;526(7574):564-8
pubmed: 26444236
Bioinformatics. 2011 Jun 15;27(12):1739-40
pubmed: 21546393
Sci Immunol. 2020 May 13;5(47):
pubmed: 32404436
Intensive Care Med. 2015 Aug;41(8):1411-23
pubmed: 26162677
J Pathol. 2013 Nov;231(3):273-89
pubmed: 24006178
Bioinformatics. 2021 Nov 18;37(22):4263-4265
pubmed: 35032393
J Am Soc Nephrol. 2014 Jan;25(1):105-18
pubmed: 24158981
Genome Res. 2019 Aug;29(8):1363-1375
pubmed: 31340985
J Am Soc Nephrol. 2007 Feb;18(2):472-84
pubmed: 17202416
J Nephrol. 2021 Apr;34(2):285-293
pubmed: 33387345
Viruses. 2021 Feb 11;13(2):
pubmed: 33670363
J Am Soc Nephrol. 2018 Jun;29(6):1690-1705
pubmed: 29739813
Cell Stem Cell. 2020 Dec 3;27(6):937-950.e9
pubmed: 33010822
Nat Chem. 2020 Jul;12(7):581
pubmed: 32555379
Nature. 2020 Nov;587(7835):555-566
pubmed: 33239795
Ann Intern Med. 2020 Aug 18;173(4):268-277
pubmed: 32374815
Nat Biotechnol. 2018 Jun;36(5):411-420
pubmed: 29608179
Cell Syst. 2015 Dec 23;1(6):417-425
pubmed: 26771021
Circ Res. 2000 Sep 1;87(5):E1-9
pubmed: 10969042
Nat Commun. 2018 Jan 2;9(1):20
pubmed: 29295995
Cell. 2020 Jun 25;181(7):1475-1488.e12
pubmed: 32479746
Biochim Biophys Acta. 2013 Jul;1832(7):931-9
pubmed: 23466594
Nat Commun. 2021 May 4;12(1):2506
pubmed: 33947851
Proc Natl Acad Sci U S A. 2020 Jul 7;117(27):15874-15883
pubmed: 32571916
J Biochem. 2016 May;159(5):481-90
pubmed: 26684586
Nat Methods. 2020 Jun;17(6):629-635
pubmed: 32483332
Cell Stem Cell. 2015 Jan 8;16(1):51-66
pubmed: 25465115
J Am Soc Nephrol. 2021 Sep;32(9):2242-2254
pubmed: 34112705
Signal Transduct Target Ther. 2020 Dec 4;5(1):283
pubmed: 33277466
J Am Soc Nephrol. 2016 Mar;27(3):781-90
pubmed: 26204899
Cell Rep. 2018 May 15;23(7):1977-1987
pubmed: 29768198
Mol Syst Biol. 2021 Jul;17(7):e9833
pubmed: 34309190
Sci Rep. 2013;3:1878
pubmed: 23698793
J Clin Invest. 2010 Nov;120(11):4040-54
pubmed: 20978353
PLoS Pathog. 2021 Feb 17;17(2):e1009225
pubmed: 33596266
Cells. 2021 Jan 07;10(1):
pubmed: 33430424
J Am Soc Nephrol. 2020 Jan;31(1):23-38
pubmed: 31537650
Nature. 2021 Jul;595(7865):107-113
pubmed: 33915569
Cell. 2020 Apr 16;181(2):271-280.e8
pubmed: 32142651
Science. 2020 Jul 3;369(6499):50-54
pubmed: 32358202
Nat Commun. 2017 Jan 16;8:14049
pubmed: 28091601
Cell. 2020 May 14;181(4):905-913.e7
pubmed: 32333836
Nat Rev Drug Discov. 2011 Dec 01;10(12):945-63
pubmed: 22129992
Clin J Am Soc Nephrol. 2020 Dec 31;16(1):14-25
pubmed: 33199414
Nat Protoc. 2020 Apr;15(4):1484-1506
pubmed: 32103204
Nat Metab. 2021 Feb;3(2):149-165
pubmed: 33536639
Nat Rev Nephrol. 2018 Jun;14(6):378-393
pubmed: 29626199
Proc Natl Acad Sci U S A. 2014 Jul 8;111(27):E2817-26
pubmed: 24958889
Nucleic Acids Res. 2020 Jun 4;48(10):e55
pubmed: 32196115
Nat Biotechnol. 2015 May;33(5):495-502
pubmed: 25867923