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SARS-CoV-2 Delta (B.1.617.2) variant replicates and induces syncytia formation in human induced pluripotent stem cell-derived macrophages
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Document Title
SARS-CoV-2 Delta (B.1.617.2) variant replicates and induces syncytia formation in human induced pluripotent stem cell-derived macrophages
Author
Thaweerattanasinp T. Wanitchang A. Saenboonrueng J. Srisutthisamphan K. Wanasen N. Sungsuwan S. Jongkaewwattana A. Chailangkarn T.
Affiliations
Virology and Cell Technology Research Team National Center for Genetic Engineering and Biotechnology (BIOTEC) National Science and Technology Development Agency (NSTDA) Pathum Thani Thailand
Type
Article
Source Title
PeerJ
ISSN
21678359
Year
2023
Volume
11
Open Access
All Open Access Gold Green
Publisher
PeerJ Inc.
DOI
10.7717/peerj.14918
Abstract
Alveolar macrophages are tissue-resident immune cells that protect epithelial cells in the alveoli from invasion by pathogens including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore the interaction between macrophages and SARS-CoV-2 is inevitable. However little is known about the role of macrophages in SARS-CoV-2 infection. Here we generated macrophages from human induced pluripotent stem cells (hiPSCs) to investigate the susceptibility of hiPSC-derived macrophages (iM8) to the authentic SARS-CoV-2 Delta (B.1.617.2) and Omicron (B.1.1.529) variants as well as their gene expression profiles of proinflammatory cytokines during infection. With undetectable angiotensin-converting enzyme 2 (ACE2) mRNA and protein expression iM8 were susceptible to productive infection with the Delta variant whereas infection of iM8 with the Omicron variant was abortive. Interestingly Delta induced cell-cell fusion or syncytia formation in iM8 which was not observed in Omicron-infected cells. However iM8 expressed moderate levels of proinflammatory cytokine genes in response to SARS-CoV-2 infection in contrast to strong upregulation of these cytokine genes in response to polarization by lipopolysaccharide (LPS) and interferon-gamma (IFN-? ). Overall our findings indicate that the SARS-CoV-2 Delta variant can replicate and cause syncytia formation in macrophages suggesting that the Delta variant can enter cells with undetectable ACE2 levels and exhibit greater fusogenicity. Copyright 2023 Thaweerattanasinp et al.
Keyword
Cytokines | Human induced pluripotent stem cells | macrophages | SARS-CoV-2 | Syncytia
Industrial Classification
Knowledge Taxonomy Level 1
Knowledge Taxonomy Level 2
Knowledge Taxonomy Level 3
License
CC BY
Rights
Authors
Publication Source
WOS