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Influenza A virus modulates ACE2 expression and SARS-CoV-2 infectivity in human cardiomyocytes.
Wu, Qian; Kumar, Naresh; Lafuse, William P; Santiagonunez Ahumada, Omar; Saljoughian, Noushin; Whetstone, Elizabeth; Zani, Ashley; Patton, Ashley K; El Refaey, Mona; Webb, Amy; Pietrzak, Maciej; Yu, Lianbo; Kc, Mahesh; Peeples, Mark E; Ganesan, Latha P; Yount, Jacob S; Rajaram, Murugesan V S.
  • Wu Q; Department of Microbial Infection and Immunity, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, USA, 43209.
  • Kumar N; Department of Microbial Infection and Immunity, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, USA, 43209.
  • Lafuse WP; Department of Microbial Infection and Immunity, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, USA, 43209.
  • Santiagonunez Ahumada O; Department of Microbial Infection and Immunity, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, USA, 43209.
  • Saljoughian N; Department of Microbial Infection and Immunity, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, USA, 43209.
  • Whetstone E; Department of Microbial Infection and Immunity, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, USA, 43209.
  • Zani A; Department of Microbial Infection and Immunity, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, USA, 43209.
  • Patton AK; Department of Pathology, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, USA, 43209.
  • El Refaey M; Department of Surgery, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, USA, 43209.
  • Webb A; Department of Biomedical Informatics, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, USA, 43209.
  • Pietrzak M; Department of Biomedical Informatics, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, USA, 43209.
  • Yu L; Department of Biomedical Informatics, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, USA, 43209.
  • Kc M; Department of Pediatrics, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, USA, 43209.
  • Peeples ME; Center for Vaccines and Immunity, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, USA, 43209.
  • Ganesan LP; Department of Pediatrics, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, USA, 43209.
  • Yount JS; Center for Vaccines and Immunity, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, USA, 43209.
  • Rajaram MVS; Department of Internal Medicine. College of Medicine, The Ohio State University, Wexner Medical Center, Columbus, OH, USA, 43210.
iScience ; : 105701, 2022 Dec 02.
Article in English | MEDLINE | ID: covidwho-2131224
ABSTRACT
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. Interestingly, 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.
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Full text: Available Collection: International databases Database: MEDLINE Language: English Journal: IScience Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Language: English Journal: IScience Year: 2022 Document Type: Article