Influenza A virus modulates ACE2 expression and SARS-CoV-2 infectivity in human cardiomyocytes
Summary: Influenza A virus (IAV) and SARS-CoV-2 virus are both acute respiratory viruses currently circulating in the human population. This study aims to determine the impact of IAV infection on SARS-CoV-2 pathogenesis and cardiomyocyte function. Infection of human bronchial epithelial cells (HBEC)...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222019745 |
| _version_ | 1828116362522787840 |
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| author | Qian Wu Naresh Kumar William P. Lafuse Omar Santiagonunez Ahumada Noushin Saljoughian Elizabeth Whetstone Ashley Zani Ashley K. Patton Mona El Refaey Amy Webb Maciej Pietrzak Lianbo Yu Mahesh KC Mark E. Peeples Latha P. Ganesan Jacob S. Yount Murugesan V.S. Rajaram |
| author_facet | Qian Wu Naresh Kumar William P. Lafuse Omar Santiagonunez Ahumada Noushin Saljoughian Elizabeth Whetstone Ashley Zani Ashley K. Patton Mona El Refaey Amy Webb Maciej Pietrzak Lianbo Yu Mahesh KC Mark E. Peeples Latha P. Ganesan Jacob S. Yount Murugesan V.S. Rajaram |
| author_sort | Qian Wu |
| collection | DOAJ |
| description | Summary: Influenza A virus (IAV) and SARS-CoV-2 virus are both acute respiratory viruses currently circulating in the human population. This study aims to determine the impact of IAV infection on SARS-CoV-2 pathogenesis and cardiomyocyte function. Infection of human bronchial epithelial cells (HBEC), A549 cells, lung fibroblasts (HLF), monocyte derived macrophages (MDMs), cardiac fibroblasts (HCF) and hiPSC-derived cardiomyocytes with IAV enhanced the expression of ACE2, the SARS-CoV-2 receptor. Similarly, IAV infection increased levels of ACE2 in the lungs of mice and humans. Of interest, we detected heavily glycosylated form of ACE2 in hiPSC-CMs and poorly glycosylated ACE2 in other cell types. Also, prior IAV infection enhances SARS-CoV-2 spike protein binding and viral entry in all cell types. However, efficient SARS-CoV-2 replication was uniquely inhibited in cardiomyocytes. Glycosylation of ACE2 correlated with enzymatic conversion of its substrate Ang II, induction of eNOS and nitric oxide production, may provide a potential mechanism for the restricted SARS-CoV-2 replication in cardiomyocytes. |
| first_indexed | 2024-04-11T12:55:38Z |
| format | Article |
| id | doaj.art-ed34aa95c1dc47edbee86bf7276a8316 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-11T12:55:38Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-ed34aa95c1dc47edbee86bf7276a83162022-12-22T04:23:05ZengElsevieriScience2589-00422022-12-012512105701Influenza A virus modulates ACE2 expression and SARS-CoV-2 infectivity in human cardiomyocytesQian Wu0Naresh Kumar1William P. Lafuse2Omar Santiagonunez Ahumada3Noushin Saljoughian4Elizabeth Whetstone5Ashley Zani6Ashley K. Patton7Mona El Refaey8Amy Webb9Maciej Pietrzak10Lianbo Yu11Mahesh KC12Mark E. Peeples13Latha P. Ganesan14Jacob S. Yount15Murugesan V.S. Rajaram16Department of Microbial Infection and Immunity, Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH 43209, USADepartment of Microbial Infection and Immunity, Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH 43209, USADepartment of Microbial Infection and Immunity, Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH 43209, USADepartment of Microbial Infection and Immunity, Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH 43209, USADepartment of Microbial Infection and Immunity, Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH 43209, USADepartment of Microbial Infection and Immunity, Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH 43209, USADepartment of Microbial Infection and Immunity, Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH 43209, USADepartment of Pathology, Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH 43209, USADepartment of Surgery, Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH 43209, USADepartment of Biomedical Informatics, Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH 43209, USADepartment of Biomedical Informatics, Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH 43209, USADepartment of Biomedical Informatics, Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH 43209, USADepartment of Pediatrics, Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH 43209, USA; Center for Vaccines and Immunity, Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH 43209, USADepartment of Pediatrics, Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH 43209, USA; Center for Vaccines and Immunity, Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH 43209, USADepartment of Internal Medicine College of Medicine, The Ohio State University, Wexner Medical Center, Columbus, OH 43210, USADepartment of Microbial Infection and Immunity, Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH 43209, USADepartment of Microbial Infection and Immunity, Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH 43209, USA; Corresponding authorSummary: Influenza A virus (IAV) and SARS-CoV-2 virus are both acute respiratory viruses currently circulating in the human population. This study aims to determine the impact of IAV infection on SARS-CoV-2 pathogenesis and cardiomyocyte function. Infection of human bronchial epithelial cells (HBEC), A549 cells, lung fibroblasts (HLF), monocyte derived macrophages (MDMs), cardiac fibroblasts (HCF) and hiPSC-derived cardiomyocytes with IAV enhanced the expression of ACE2, the SARS-CoV-2 receptor. Similarly, IAV infection increased levels of ACE2 in the lungs of mice and humans. Of interest, we detected heavily glycosylated form of ACE2 in hiPSC-CMs and poorly glycosylated ACE2 in other cell types. Also, prior IAV infection enhances SARS-CoV-2 spike protein binding and viral entry in all cell types. However, efficient SARS-CoV-2 replication was uniquely inhibited in cardiomyocytes. Glycosylation of ACE2 correlated with enzymatic conversion of its substrate Ang II, induction of eNOS and nitric oxide production, may provide a potential mechanism for the restricted SARS-CoV-2 replication in cardiomyocytes.http://www.sciencedirect.com/science/article/pii/S2589004222019745ProteinVirologyCell biology |
| spellingShingle | Qian Wu Naresh Kumar William P. Lafuse Omar Santiagonunez Ahumada Noushin Saljoughian Elizabeth Whetstone Ashley Zani Ashley K. Patton Mona El Refaey Amy Webb Maciej Pietrzak Lianbo Yu Mahesh KC Mark E. Peeples Latha P. Ganesan Jacob S. Yount Murugesan V.S. Rajaram Influenza A virus modulates ACE2 expression and SARS-CoV-2 infectivity in human cardiomyocytes iScience Protein Virology Cell biology |
| title | Influenza A virus modulates ACE2 expression and SARS-CoV-2 infectivity in human cardiomyocytes |
| title_full | Influenza A virus modulates ACE2 expression and SARS-CoV-2 infectivity in human cardiomyocytes |
| title_fullStr | Influenza A virus modulates ACE2 expression and SARS-CoV-2 infectivity in human cardiomyocytes |
| title_full_unstemmed | Influenza A virus modulates ACE2 expression and SARS-CoV-2 infectivity in human cardiomyocytes |
| title_short | Influenza A virus modulates ACE2 expression and SARS-CoV-2 infectivity in human cardiomyocytes |
| title_sort | influenza a virus modulates ace2 expression and sars cov 2 infectivity in human cardiomyocytes |
| topic | Protein Virology Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222019745 |
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