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Cross-validation of SARS-CoV-2 responses in kidney organoids and clinical populations.
Helms, Louisa; Marchiano, Silvia; Stanaway, Ian B; Hsiang, Tien-Ying; Juliar, Benjamin A; Saini, Shally; Zhao, Yan Ting; Khanna, Akshita; Menon, Rajasree; Alakwaa, Fadhl; Mikacenic, Carmen; Morrell, Eric D; Wurfel, Mark M; Kretzler, Matthias; Harder, Jennifer L; Murry, Charles E; Himmelfarb, Jonathan; Ruohola-Baker, Hannele; Bhatraju, Pavan K; Gale, Michael; Freedman, Benjamin S.
  • Helms L; Department of Medicine.
  • Marchiano S; Division of Nephrology.
  • Stanaway IB; Kidney Research Institute.
  • Hsiang TY; Institute for Stem Cell and Regenerative Medicine.
  • Juliar BA; Department of Laboratory Medicine and Pathology.
  • Saini S; Department of Medicine.
  • Zhao YT; Institute for Stem Cell and Regenerative Medicine.
  • Khanna A; Department of Laboratory Medicine and Pathology.
  • Menon R; Division of Cardiology.
  • Alakwaa F; Center for Cardiovascular Biology.
  • Mikacenic C; Department of Medicine.
  • Morrell ED; Division of Nephrology.
  • Wurfel MM; Kidney Research Institute.
  • Kretzler M; Center for Innate Immunity and Immune Disease, Department of Immunology.
  • Harder JL; Department of Medicine.
  • Murry CE; Division of Nephrology.
  • Himmelfarb J; Kidney Research Institute.
  • Ruohola-Baker H; Institute for Stem Cell and Regenerative Medicine.
  • Bhatraju PK; Institute for Stem Cell and Regenerative Medicine.
  • Gale M; Department of Biochemistry; and.
  • Freedman BS; Institute for Stem Cell and Regenerative Medicine.
JCI Insight ; 6(24)2021 12 22.
Article in English | MEDLINE | ID: covidwho-1518199
ABSTRACT
Kidneys are critical target organs of COVID-19, but susceptibility and responses to infection remain poorly understood. Here, we combine SARS-CoV-2 variants with genome-edited kidney organoids and clinical data to investigate tropism, mechanism, and therapeutics. SARS-CoV-2 specifically infects organoid proximal tubules among diverse cell types. Infections produce replicating virus, apoptosis, and disrupted cell morphology, features of which are revealed in the context of polycystic kidney disease. Cross-validation of gene expression patterns in organoids reflects proteomic signatures of COVID-19 in the urine of critically ill patients indicating interferon pathway upregulation. SARS-CoV-2 viral variants alpha, beta, gamma, kappa, and delta exhibit comparable levels of infection in organoids. Infection is ameliorated in ACE2-/- organoids and blocked via treatment with de novo-designed spike binder peptides. Collectively, these studies clarify the impact of kidney infection in COVID-19 as reflected in organoids and clinical populations, enabling assessment of viral fitness and emerging therapies.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Organoids / Acute Kidney Injury / SARS-CoV-2 / COVID-19 / Kidney / Kidney Tubules, Proximal Type of study: Prognostic study / Randomized controlled trials Topics: Long Covid / Variants Language: English Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Organoids / Acute Kidney Injury / SARS-CoV-2 / COVID-19 / Kidney / Kidney Tubules, Proximal Type of study: Prognostic study / Randomized controlled trials Topics: Long Covid / Variants Language: English Year: 2021 Document Type: Article