Human Kidney Spheroids and Monolayers Provide Insights into SARS-CoV-2 Renal Interactions.
Acute Kidney Injury
/ etiology
Animals
COVID-19
/ complications
Cells, Cultured
Chlorocebus aethiops
Cohort Studies
Cytopathogenic Effect, Viral
Epithelial Cells
/ pathology
Host Microbial Interactions
Humans
Interferon Type I
/ metabolism
Kidney
/ immunology
Mice
Mice, Inbred NOD
Mice, SCID
Models, Biological
Pandemics
Receptors, Virus
/ metabolism
Retrospective Studies
SARS-CoV-2
/ pathogenicity
Spheroids, Cellular
/ pathology
Vero Cells
Virus Replication
COVID-19
SARS-CoV-2
acute kidney injury
cytopathic damage
human tubular kidney cells
interferon pathway
kidney spheroids
kidney stem cells
renal progenitors
renal tubular epithelial cells
Journal
Journal of the American Society of Nephrology : JASN
ISSN: 1533-3450
Titre abrégé: J Am Soc Nephrol
Pays: United States
ID NLM: 9013836
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
01
11
2020
accepted:
22
04
2021
pubmed:
12
6
2021
medline:
18
9
2021
entrez:
11
6
2021
Statut:
ppublish
Résumé
Although coronavirus disease 2019 (COVID-19) causes significan t morbidity, mainly from pulmonary involvement, extrapulmonary symptoms are also major componen ts of the disease. Kidney disease, usually presenting as AKI, is particularly severe among patients with COVID-19. It is unknown, however, whether such injury results from direct kidney infection with COVID-19's causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or from indirect mechanisms. Using We demonstrated that viral entry molecules and high baseline levels of type 1 IFN-related molecules were present in monolayers and kidney spheroids. Although both models support viral infection and replication, they did not exhibit a cytopathic effect and cell death, outcomes that were strongly present in SARS-CoV-2-infected controls (African green monkey kidney clone E6 [Vero E6] cultures). A comparison of monolayer and spheroid cultures demonstrated higher infectivity and replication of SARS-CoV-2 in actively proliferating monolayers, although the spheroid cultures exhibited high er levels of ACE2. Monolayers exhibited elevation of some tubular injury molecules-including molecules related to fibrosis (COL1A1 and STAT6) and dedifferentiation (SNAI2)-and a loss of cell identity, evident by reduction in megalin (LRP2). The three-dimensional spheroids were less prone to such injury. SARS-CoV-2 can infect kidney cells without a cytopathic effect. AKI-induced cellular proliferation may potentially intensify infectivity and tubular damage by SARS-CoV-2, suggesting that early intervention in AKI is warranted to help minimize kidney infection.
Sections du résumé
BACKGROUND
Although coronavirus disease 2019 (COVID-19) causes significan t morbidity, mainly from pulmonary involvement, extrapulmonary symptoms are also major componen ts of the disease. Kidney disease, usually presenting as AKI, is particularly severe among patients with COVID-19. It is unknown, however, whether such injury results from direct kidney infection with COVID-19's causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or from indirect mechanisms.
METHODS
Using
RESULTS
We demonstrated that viral entry molecules and high baseline levels of type 1 IFN-related molecules were present in monolayers and kidney spheroids. Although both models support viral infection and replication, they did not exhibit a cytopathic effect and cell death, outcomes that were strongly present in SARS-CoV-2-infected controls (African green monkey kidney clone E6 [Vero E6] cultures). A comparison of monolayer and spheroid cultures demonstrated higher infectivity and replication of SARS-CoV-2 in actively proliferating monolayers, although the spheroid cultures exhibited high er levels of ACE2. Monolayers exhibited elevation of some tubular injury molecules-including molecules related to fibrosis (COL1A1 and STAT6) and dedifferentiation (SNAI2)-and a loss of cell identity, evident by reduction in megalin (LRP2). The three-dimensional spheroids were less prone to such injury.
CONCLUSIONS
SARS-CoV-2 can infect kidney cells without a cytopathic effect. AKI-induced cellular proliferation may potentially intensify infectivity and tubular damage by SARS-CoV-2, suggesting that early intervention in AKI is warranted to help minimize kidney infection.
Identifiants
pubmed: 34112705
pii: 00001751-202109000-00019
doi: 10.1681/ASN.2020111546
pmc: PMC8729846
doi:
Substances chimiques
Interferon Type I
0
Receptors, Virus
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2242-2254Informations de copyright
Copyright © 2021 by the American Society of Nephrology.
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