SARS-CoV-2 Delta (B.1.617.2) variant replicates and induces syncytia formation in human induced pluripotent stem cell-derived macrophages

PeerJ

article

Theeradej Thaweerattanasinp¹  Asawin Wanitchang¹  Janya Saenboonrueng¹  Kanjana Srisutthisamphan¹  Nanchaya Wanasen¹  Suttipun Sungsuwan¹  Anan Jongkaewwattana¹  Thanathom Chailangkarn¹ 

[1] Virology and Cell Technology Research Team, National Center for Genetic Engineering and Biotechnology ,(BIOTEC), National Science and Technology Development Agency

关键词: Macrophages;    SARS-CoV-2;    Syncytia;    Cytokines;    Human induced pluripotent stem cells;   

DOI  :  10.7717/peerj.14918

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

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 (iMΦ) 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, iMΦ were susceptible to productive infection with the Delta variant, whereas infection of iMΦ with the Omicron variant was abortive. Interestingly, Delta induced cell-cell fusion or syncytia formation in iMΦ, which was not observed in Omicron-infected cells. However, iMΦ 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-γ). 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.

【 授权许可】

CC BY