SARS-CoV-2 Delta spike protein enhances the viral fusogenicity and inflammatory cytokine production
The Delta variant had spread globally in 2021 and caused more serious disease than the original virus and Omicron variant. In this study, we investigated several virological features of Delta spike protein (SPDelta), including protein maturation, its impact on viral entry of pseudovirus and cell-cel...
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Published in | iScience Vol. 25; no. 8; p. 104759 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Elsevier Inc
19.08.2022
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | The Delta variant had spread globally in 2021 and caused more serious disease than the original virus and Omicron variant. In this study, we investigated several virological features of Delta spike protein (SPDelta), including protein maturation, its impact on viral entry of pseudovirus and cell-cell fusion, and its induction of inflammatory cytokine production in human macrophages and dendritic cells. The results showed that SPΔCDelta exhibited enhanced S1/S2 cleavage in cells and pseudotyped virus-like particles (PVLPs). Further, SPΔCDelta elevated pseudovirus entry in human lung cell lines and significantly enhanced syncytia formation. Furthermore, we revealed that SPΔCDelta-PVLPs had stronger effects on stimulating NF-κB and AP-1 signaling in human monocytic THP1 cells and induced significantly higher levels of proinflammatory cytokine, such as TNF-α, IL-1β, and IL-6, released from human macrophages and dendritic cells. Overall, these studies provide evidence to support the important role of SPΔCDelta during virus infection, transmission, and pathogenesis.
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•SARS-CoV-2 Delta-SP exhibits enhanced cleavage and more efficient pseudovirus entry•Delta-SP enhances syncytia formation in A549 cells expressing ACE2•Delta-SP stimulates higher NF-κB and AP1 signaling pathway activities•Delta-SP stimulates higher proinflammatory cytokine production in MDMs and MDDCs
Virology; Molecular biology |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally Lead contact |
ISSN: | 2589-0042 2589-0042 |
DOI: | 10.1016/j.isci.2022.104759 |