SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis
SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis
Abstract Epidemiological studies of the COVID-19 pandemic have revealed evidence of cardiac involvement and documented that myocardial injury and myocarditis are predictors of poor outcomes. Nonetheless, little is understood regarding SARS-CoV-2 tropism within the heart and whether cardiac complications result directly from myocardial infection. Here, we develop a human engineered heart tissue model and demonstrate that SARS-CoV-2 selectively infects cardiomyocytes. Viral infection is dependent on expression of angiotensin-I converting enzyme 2 (ACE2) and endosomal cysteine proteases, suggesting an endosomal mechanism of cell entry. After infection with SARS-CoV-2, engineered tissues display typical features of myocarditis, including cardiomyocyte cell death, impaired cardiac contractility, and innate immune cell activation. Consistent with these findings, autopsy tissue obtained from individuals with COVID-19 myocarditis demonstrated cardiomyocyte infection, cell death, and macrophage-predominate immune cell infiltrate. These findings establish human cardiomyocyte tropism for SARS-CoV-2 and provide an experimental platform for interrogating and mitigating cardiac complications of COVID-19.
Bailey Adam L.、Dmytrenko Oleksandr、Penna Vinay、Heck Kent A.、Simpson Leo、Saririan Mehrdad、Hobohm Dan、Fitzpatrick James A.、Shi Pei-Yong、Schmidt Constanze、Greenberg Michael J.、Nair Ajith P.、Lavine Kory J.、Lai Lulu、Leuschner Florian、Gi Weng-Tein、Ma Pan、Liu Jing、Rali Aniket S.、Bredemeyer Andrea L.、Lin Chieh-Yu、Brooks Erin、Winkler Emma S.、Greenberg Lina、Diamond Michael S.、Xie Xuping、Sviben Sanja、Hinson J. Travis、Stump W. Tom
Department of Pathology and Immunology, Washington University School of MedicineDepartment of Medicine, Washington University School of MedicineDepartment of Medicine, Washington University School of MedicineDepartment of Pathology, Baylor College of MedicineDepartment of Medicine, Baylor College of MedicineValleywise Health/Creighton UniversityValleywise Health/Creighton UniversityWashington University Center for Cellular Imaging, Washington University School of Medicine||Departments of Neuroscience, Cell Biology & Physiology, and Biomedical Engineering, Washington University School of MedicineDepartment of Biochemistry and Molecular Biology, University of Texas Medical BranchDepartment of Internal Medicine III, University Hospital Heidelberg, University of HeidelbergDepartment of Biochemistry and Molecular Biophysics, Washington University School of MedicineDepartment of Medicine, Baylor College of MedicineDepartment of Pathology and Immunology, Washington University School of Medicine||Department of Medicine, Washington University School of Medicine||Department of Developmental Biology, Washington University School of MedicineDepartment of Medicine, Washington University School of MedicineDepartment of Internal Medicine III, University Hospital Heidelberg, University of HeidelbergDepartment of Internal Medicine III, University Hospital Heidelberg, University of HeidelbergDepartment of Medicine, Washington University School of MedicineDepartment of Medicine, Washington University School of MedicineDepartment of Medicine, Vanderbilt UniversityDepartment of Medicine, Washington University School of MedicineDepartment of Pathology and Immunology, Washington University School of MedicineDepartment of Pathology & Laboratory Medicine, University of Wisconsin Hospital and ClinicsDepartment of Pathology and Immunology, Washington University School of MedicineDepartment of Biochemistry and Molecular Biophysics, Washington University School of MedicineDepartment of Pathology and Immunology, Washington University School of Medicine||Department of Medicine, Washington University School of Medicine||Department of Molecular Microbiology, Washington University School of MedicineDepartment of Biochemistry and Molecular Biology, University of Texas Medical BranchWashington University Center for Cellular Imaging, Washington University School of MedicineDepartments of Cardiology and Genetics and Genome Sciences, UConn Health||The Jackson Laboratory for Genomic MedicineDepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine
基础医学生物科学研究方法、生物科学研究技术生理学
SARS-CoV-2COVID-19MyocarditisEngineered Heart TissueCardiomyocyteMacrophage
Bailey Adam L.,Dmytrenko Oleksandr,Penna Vinay,Heck Kent A.,Simpson Leo,Saririan Mehrdad,Hobohm Dan,Fitzpatrick James A.,Shi Pei-Yong,Schmidt Constanze,Greenberg Michael J.,Nair Ajith P.,Lavine Kory J.,Lai Lulu,Leuschner Florian,Gi Weng-Tein,Ma Pan,Liu Jing,Rali Aniket S.,Bredemeyer Andrea L.,Lin Chieh-Yu,Brooks Erin,Winkler Emma S.,Greenberg Lina,Diamond Michael S.,Xie Xuping,Sviben Sanja,Hinson J. Travis,Stump W. Tom.SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2020.11.04.364315.点此复制
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