SARS-CoV-2 Delta spike protein enhances the viral fusogenicity and inflammatory cytokine production

Zhujun Ao; Maggie Jing Ouyang; Titus Abiola Olukitibi; Xiaojian Yao

doi:10.1016/j.isci.2022.104759

SARS-CoV-2 Delta spike protein enhances the viral fusogenicity and inflammatory cytokine production

iScience. 2022 Aug 19;25(8):104759. doi: 10.1016/j.isci.2022.104759. Epub 2022 Jul 14.

Authors

Zhujun Ao¹, Maggie Jing Ouyang¹, Titus Abiola Olukitibi¹, Xiaojian Yao¹

Affiliation

¹ Laboratory of Molecular Human Retrovirology, Department of Medical Microbiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.

Abstract

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 (SP_Delta), 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 SPΔC_Delta exhibited enhanced S1/S2 cleavage in cells and pseudotyped virus-like particles (PVLPs). Further, SPΔC_Delta elevated pseudovirus entry in human lung cell lines and significantly enhanced syncytia formation. Furthermore, we revealed that SPΔC_Delta-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 SPΔC_Delta during virus infection, transmission, and pathogenesis.

Keywords: Molecular biology; Virology.