Detection of viral RNA fragments in human iPSC cardiomyocytes following treatment with extracellular vesicles from SARS-
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Detection of viral RNA fragments in human iPSC cardiomyocytes following treatment with extracellular vesicles from SARS-CoV-2 coding sequence overexpressing lung epithelial cells Youjeong Kwon1†, Sarath Babu Nukala1†, Shubhi Srivastava1†, Hiroe Miyamoto1, Nur Izzah Ismail2,3,4, Jordan Jousma1, Jalees Rehman1,5, Sang-Bing Ong2,3,4*, Won Hee Lee6* and Sang-Ging Ong1,5*
Abstract Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global pandemic. The prevalence/severity of COVID-19 is higher among patients with cardiovascular risk factors. Despite the expression of angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV-2 infection, in cardiomyocytes, there has been no conclusive evidence of direct viral infection although the presence of viral genome within COVID-19 patients’ hearts has been reported. Here, we overexpressed SARS-CoV-2 genes in A549 lung epithelial cells. We then isolated extracellular vesicles (EVs) and detected the presence of viral RNA within these EVs. We observed that human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are receptive to these EVs, and viral genes were detectable in the cardiomyocytes. Accordingly, the uptake of viral RNAharboring EVs led to an upregulation of inflammation-related genes in hiPSC-CMs. Thus, our findings indicate that SARS-CoV-2 RNA containing EVs represents an indirect route of viral RNA entry into cardiomyocytes. Keywords: COVID-19, Extracellular vesicles, iPSCs, Stem cells, Cardiomyocytes
* Correspondence: [email protected]; [email protected]; [email protected] † Youjeong Kwon, Sarath Babu Nukala and Shubhi Srivastava contributed equally to this work. 2 Centre for Cardiovascular Genomics and Medicine, Lui Che Woo Institute of Innovative Medicine, Chinese University of Hong Kong (CUHK), Hong Kong, Hong Kong SAR 6 Department of Basic Medical Sciences, University of Arizona College of Medicine – Phoenix, 425 N 5th St., Bldg ABC1 Rm 426, Phoenix, AZ 85004, USA 1 Department of Pharmacology, The University of Illinois College of Medicine, 909 S Wolcott Ave, COMRB 4097, Chicago, IL 60612, USA Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a c
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