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bioRxiv · 10.1101/2021.11.23.469765

SARS-CoV-2 Delta Spike Protein Enhances the Viral Fusogenicity and Inflammatory Cytokine Production

Ao, Z.·Ouyang, M. J.·Olukitibi, T. A.·Yao, X.
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Abstract

The Delta variant is now the most dominant and virulent SARS-CoV-2 variant of concern (VOC). In this study, we investigated several virological features of Delta spike protein (SPDelta), including protein maturation and its impact on viral entry of cell-free pseudotyped virus, cell-cell fusion ability and its induction of inflammatory cytokine production in human macrophages and dendritic cells. The results showed that SP{Delta}CDelta exhibited enhanced S1/S2 cleavage in cells and pseudotyped virus-like particles (PVLPs). We further showed that SP{Delta}CDelta elevated pseudovirus infection in human lung cell lines and mediated significantly enhanced syncytia formation. Furthermore, we revealed that SP{Delta}CDelta-PVLPs had stronger effects on stimulating NF-{kappa}B and AP-1 signaling in human monocytic THP1 cells and induced significantly higher levels of pro-inflammatory cytokine, such as TNF-, IL-1{beta} and IL-6, released from human macrophages and dendritic cells. Overall, these studies provide evidence to support the important role of SP{Delta}CDelta during virus infection, transmission and pathogenesis.

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Ao, Z., Ouyang, M. J., Olukitibi, T. A., Yao, X.. 2021-11-24. SARS-CoV-2 Delta Spike Protein Enhances the Viral Fusogenicity and Inflammatory Cytokine Production. https://doi.org/10.1101/2021.11.23.469765

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