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 Kwon, Sarath Babu Nukala, Shubhi Srivastava, Hiroe Miyamoto, Nur Izzah Ismail, Jordan Jousma, Jalees Rehman, Sang Bing Ong, Won Hee Lee, Sang Ging Ong

Research output: Contribution to journalLetterpeer-review

18 Scopus citations

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 RNA-harboring 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.

Original languageEnglish (US)
Article number514
JournalStem Cell Research and Therapy
Volume11
Issue number1
DOIs
StatePublished - Dec 2020
Externally publishedYes

Keywords

  • COVID-19
  • Cardiomyocytes
  • Extracellular vesicles
  • Stem cells
  • iPSCs

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Cell Biology

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