SARS-CoV-2 Infects Human Pluripotent Stem Cell-Derived Cardiomyocytes, Impairing Electrical and Mechanical Function.

COVID-19 / virology Cells, Cultured Humans Induced Pluripotent Stem Cells / virology Myocytes, Cardiac / virology RNA Splicing / genetics RNA, Messenger / genetics SARS-CoV-2 / genetics Virus Internalization
COVID-19 SARS-CoV-2 arrhythmias and heart failure cardiac infection cardiovascular disease hESC-CMs hPSC-CMs human pluripotent stem cell-derived cardiomyocytes viral myocarditis

Journal

Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300

Informations de publication

Date de publication:
09 03 2021
Historique:
received: 18 01 2021
revised: 08 02 2021
accepted: 09 02 2021
pubmed: 4 3 2021
medline: 25 3 2021
entrez: 3 3 2021
Statut: ppublish

Résumé

COVID-19 patients often develop severe cardiovascular complications, but it remains unclear if these are caused directly by viral infection or are secondary to a systemic response. Here, we examine the cardiac tropism of SARS-CoV-2 in human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and smooth muscle cells (hPSC-SMCs). We find that that SARS-CoV-2 selectively infects hPSC-CMs through the viral receptor ACE2, whereas in hPSC-SMCs there is minimal viral entry or replication. After entry into cardiomyocytes, SARS-CoV-2 is assembled in lysosome-like vesicles and egresses via bulk exocytosis. The viral transcripts become a large fraction of cellular mRNA while host gene expression shifts from oxidative to glycolytic metabolism and upregulates chromatin modification and RNA splicing pathways. Most importantly, viral infection of hPSC-CMs progressively impairs both their electrophysiological and contractile function, and causes widespread cell death. These data support the hypothesis that COVID-19-related cardiac symptoms can result from a direct cardiotoxic effect of SARS-CoV-2.

Identifiants

DOI: 10.1016/j.stemcr.2021.02.008 PMID: 33657418 PMC: PMC7881699
pubmed: 33657418
pii: S2213-6711(21)00088-6
doi: 10.1016/j.stemcr.2021.02.008
pmc: PMC7881699
pii:
doi:

Substances chimiques

RNA, Messenger 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

478-492

Subventions

Organisme : Medical Research Council
ID : MC_PC_17230
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL128362
Pays : United States
Organisme : NIH HHS
ID : P51 OD010425
Pays : United States
Organisme : Wellcome Trust
ID : 203568/Z/16/Z
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : U01 AI151698
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL149734
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL146868
Pays : United States
Organisme : British Heart Foundation
ID : FS/13/65/30441
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : UM1 AI148684
Pays : United States

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

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Auteurs

Silvia Marchiano (S)

Department of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Center for Cardiovascular Biology, University of Washington, 850 Republican Street, Brotman Building, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Seattle, WA 98109, USA.

Tien-Ying Hsiang (TY)

Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA.

Akshita Khanna (A)

Department of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Center for Cardiovascular Biology, University of Washington, 850 Republican Street, Brotman Building, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Seattle, WA 98109, USA.

Ty Higashi (T)

Department of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Center for Cardiovascular Biology, University of Washington, 850 Republican Street, Brotman Building, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Seattle, WA 98109, USA; Department of Mechanical Engineering, University of Washington, 3720 15th Avenue NE, Seattle, WA 98105, USA.

Leanne S Whitmore (LS)

Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA.

Johannes Bargehr (J)

Wellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Puddicombe Way, CB2 0AW Cambridge, UK; Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke's Hospital, ACCI Level 6, Box 110, Hills Road, Cambridge CB2 0QQ, UK.

Hongorzul Davaapil (H)

Wellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Puddicombe Way, CB2 0AW Cambridge, UK; Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke's Hospital, ACCI Level 6, Box 110, Hills Road, Cambridge CB2 0QQ, UK.

Jean Chang (J)

Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA.

Elise Smith (E)

Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA.

Lay Ping Ong (LP)

Wellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Puddicombe Way, CB2 0AW Cambridge, UK; Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke's Hospital, ACCI Level 6, Box 110, Hills Road, Cambridge CB2 0QQ, UK.

Maria Colzani (M)

Wellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Puddicombe Way, CB2 0AW Cambridge, UK; Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke's Hospital, ACCI Level 6, Box 110, Hills Road, Cambridge CB2 0QQ, UK.

Hans Reinecke (H)

Department of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Center for Cardiovascular Biology, University of Washington, 850 Republican Street, Brotman Building, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Seattle, WA 98109, USA.

Xiulan Yang (X)

Department of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Center for Cardiovascular Biology, University of Washington, 850 Republican Street, Brotman Building, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Seattle, WA 98109, USA.

Lil Pabon (L)

Department of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Center for Cardiovascular Biology, University of Washington, 850 Republican Street, Brotman Building, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Seattle, WA 98109, USA; Sana Biotechnology, 188 E Blaine Street, Seattle, WA 98102, USA.

Sanjay Sinha (S)

Wellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Puddicombe Way, CB2 0AW Cambridge, UK; Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke's Hospital, ACCI Level 6, Box 110, Hills Road, Cambridge CB2 0QQ, UK.

Behzad Najafian (B)

Department of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA.

Nathan J Sniadecki (NJ)

Department of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Center for Cardiovascular Biology, University of Washington, 850 Republican Street, Brotman Building, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Seattle, WA 98109, USA; Department of Mechanical Engineering, University of Washington, 3720 15th Avenue NE, Seattle, WA 98105, USA; Department of Bioengineering, University of Washington, 3720 15th Avenue NE, Seattle, WA 98105, USA.

Alessandro Bertero (A)

Department of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Center for Cardiovascular Biology, University of Washington, 850 Republican Street, Brotman Building, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Seattle, WA 98109, USA.

Michael Gale (M)

Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA. Electronic address: mgale@uw.edu.

Charles E Murry (CE)

Department of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Center for Cardiovascular Biology, University of Washington, 850 Republican Street, Brotman Building, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Seattle, WA 98109, USA; Sana Biotechnology, 188 E Blaine Street, Seattle, WA 98102, USA; Department of Bioengineering, University of Washington, 3720 15th Avenue NE, Seattle, WA 98105, USA; Department of Medicine/Cardiology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA. Electronic address: murry@uw.edu.

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Recherchemedicale.com › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Pneumopathie infectieuse › Pneumopathie virale › COVID-19 › SARS-CoV-2 Infects Human Pluripotent Stem...
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Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › SARS-CoV-2 Infects Human Pluripotent Stem...
Recherchemedicale.com › Cellules › Cellules souches › Cellules souches pluripotentes › Cellules souches pluripotentes induites › SARS-CoV-2 Infects Human Pluripotent Stem...
Recherchemedicale.com › Cellules › Cellules musculaires › Myocytes cardiaques › SARS-CoV-2 Infects Human Pluripotent Stem...
Recherchemedicale.com › Phénomènes génétiques › Régulation de l'expression des gènes › Maturation post-transcriptionnelle des ARN › Épissage des ARN › SARS-CoV-2 Infects Human Pluripotent Stem...
Recherchemedicale.com › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN messager › SARS-CoV-2 Infects Human Pluripotent Stem...
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Recherchemedicale.com › Phénomènes microbiologiques › Phénomènes physiologiques viraux › Pénétration virale › SARS-CoV-2 Infects Human Pluripotent Stem...